Atherosclerosis(AS)is a progressive inflammatory disease,and thrombosis most likely leads to cardiovascular morbidity and mortality globally.Thrombolytic drugs alone cannot completely prevent thrombotic events,and tre...Atherosclerosis(AS)is a progressive inflammatory disease,and thrombosis most likely leads to cardiovascular morbidity and mortality globally.Thrombolytic drugs alone cannot completely prevent thrombotic events,and treatments targeting thrombosis also need to regulate the inflammatory process.Based on the dynamic pathological development of AS,biomimetic thrombus-targeted nanoparticles HMTL@PM were prepared.Hirudin and lumbrukinase,effective substances of traditional Chinese medicine,were self-assembled under the action of tannic acid and Mn^(2+).HMTL@PM dissociated in the weakly acidic microenvironment of atherosclerosis and exhibited excellent therapeutic effects,including alleviating inflammation,dissolving thrombus,anticoagulation,and promoting cholesterol efflux.HMTL@PM effectively regulated the progression of AS and provided a newperspective for the development of drug delivery systems for AS therapy,which holds important research significance for reducing the mortality of cardiovascular and cerebrovascular diseases.展开更多
Background:Aortic atherosclerosis increases the risk of embolic events under extracorporeal circulation(ECC).To evaluate the hemodynamic impact of ECC on atheromatous plaques,an atherosclerosis animal model,which is a...Background:Aortic atherosclerosis increases the risk of embolic events under extracorporeal circulation(ECC).To evaluate the hemodynamic impact of ECC on atheromatous plaques,an atherosclerosis animal model,which is also eligible for ECC,is required.Methods:Twenty-nine New Zealand White rabbits received a pro-atherosclerotic diet(group diet,n=10),a pro-atherosclerotic diet and additional intraaortic balloon insufflation injury(group BI,n=9),or served as controls(n=10).After 3 or 6 months,aortic explants were analyzed by(immuno-)histology and RT-PCR.Results:Blood serum analyses revealed increased cholesterol-levels in groups diet and BI compared to controls(3 months:p=0.03 each,6 months:p<0.0001 each).Aortic inflammatory infiltration was significantly enhanced in groups diet(CD3 at 3 months:p<0.0001,6 months:p=0.02;CD68 at 3 months:p=0.01)and BI(CD3 at 3 months:p<0.0001,6 months:p=0.03;CD68 at 3 months:p=0.04,6 months:p=0.02).Increased intima hyperplasia occurred in both groups(p<0.0001 each).Macroscopic analyses after 3 and 6 months showed ubiquitous lumen-narrowing aortic plaques.Calcification of the intima and media was increased in groups diet(intima:p<0.0001 at 3 and 6 months;media at 3 months:p<0.0001,6 months:p=0.01)and BI(intima:p<0.0001 at 3 and 6 months;media at 3 months:p<0.0001,6 months:p=0.02).Extensive lipid accumulation was found in the intima in both treatment groups(p<0.0001 each).Conclusions:A rabbit model with high aortic calcific plaque burden—diet-induced with no implicit need of an additional intimal injury by an intraaortic balloon insufflation due to comparable outcome—exhibiting multiple pathophysiological aspects of human atherosclerosis has been designed and thoroughly characterized.It is suitable for use in future studies on the interaction between atherosclerotic plaques and the arterial blood flow under ECC.展开更多
Background:Atherosclerosis(AS),the primary pathological foundation of cardiovascular diseases,is characterized by intricate processes including inflammation,lipid metabolism disorders,and pyroptosis.While the traditio...Background:Atherosclerosis(AS),the primary pathological foundation of cardiovascular diseases,is characterized by intricate processes including inflammation,lipid metabolism disorders,and pyroptosis.While the traditional Chinese medicine compound Dingxin Recipe(DXR)has demonstrated definitive clinical efficacy in treating AS,its therapeutic mechanisms remain unclear.This study employed an integrated approach combining network pharmacology,molecular docking,and molecular dynamics simulations(MDS)to investigate DXR’s anti-AS mechanisms.Methods:Active ingredients and targets of DXR were identified and screened using databases such as GeneCards,OMIM,and TCMSP.An“ingredient-target-disease”network was constructed to visualize these interactions.Molecular docking was utilized to assess the binding affinity between key ingredients and their respective targets.Additionally,MDS were conducted to analyze the stability of these complexes,providing robust evidence for further clinical applications and in-depth research.Results:Through network pharmacology analysis,we identified 99 active drug components,934 gene targets,and 1463 disease targets associated with DXR.Protein-protein interaction analysis revealed central regulatory nodes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that these components primarily modulate processes such as inflammatory response and transcription factor activation,and are closely linked to the AGERAGE signaling pathway,lipid metabolism,and atherosclerosis pathways.Molecular docking confirmed strong binding potential between the components and their targets,while MDS further validated the stability of these interactions.Conclusion:This study elucidates that the active ingredients in DXR alleviate AS by mitigating inflammatory responses and inhibiting pyroptosis through the suppression of inflammatory factor release.These findings provide a scientific foundation for the clinical application of DXR in AS treatment.展开更多
The host-microbe co-metabolism system,generating diverse exogenous and endogenous bioactive molecules that influence the host’s immune and metabolic functions,plays a crucial role in the pathogenesis of atheroscleros...The host-microbe co-metabolism system,generating diverse exogenous and endogenous bioactive molecules that influence the host’s immune and metabolic functions,plays a crucial role in the pathogenesis of atherosclerosis.Recent studies have elucidated the interaction between natural medicines and this co-metabolism system.Upon oral administration,natural medicine ingredients can undergo transformation by gut microbiota,potentially enhancing their bioavailability or anti-atherogenic efficacy.Furthermore,natural medicines can exert anti-atherogenic effects via modulation of endogenous host-microbe co-metabolism.This review presents an updated understanding of the dual association between natural medicines and host-microbe co-metabolites.It explores the critical function of microbial exogenous metabolites derived from natural medicines and uncovers the mechanisms underlying natural medicines’intervention on key nodes of endogenous host-microbe co-metabolism.These insights may offer new perspectives for cardiovascular disease(CVD)treatment and guide future drug discovery efforts.展开更多
Red wine has a good potential for alleviating atherosclerosis,but the mechanisms related to hepatointestinal circulation remain to be elucidated.This study showed that administration of a high-polyphenol red wine(16 m...Red wine has a good potential for alleviating atherosclerosis,but the mechanisms related to hepatointestinal circulation remain to be elucidated.This study showed that administration of a high-polyphenol red wine(16 mL/(kg·day))for 16 weeks significantly reduced the atherosclerotic lesion in high-fat diet-fed ApoE^(-/-)mice.The total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C)levels of plasma were lowered by 11.54%and 18.98%.The pro-inflammatory cytokines including interleukin-6(IL-6)and tumor necrosis factorα(TNF-α)levels were decreased by 27.59%and 31.92%.Red wine also reduced triglyceride(TG)level and lipid deposition in the liver,and increased the concentration of total bile acids(TBA).Untargeted metabolomics analysis indicated that red wine modulated the disorder of liver metabolism by regulating sphingolipid signaling pathway,sphingolipid metabolism,glycerophosphlipid metabolism,choline metabolism and bile secretion.16S rRNA sequencing revealed that red wine increased the abundance of Akkermansia and Bifidobacterium and reduced the abundance of Mucispirillum,Romboutsia,Lactobacillus,Bilophila and Blautia,along with the increased concentrations of short-chain fatty acids(SCFAs)in feces.These findings indicated that red wine could exert anti-atherosclerotic effect by regulating gut microbiota,restoring SCFAs,alleviating liver metabolic disorders.展开更多
Objective Atherosclerosis involves not only the narrowing of blood vessels and plaque accumulation but also changes in plaque composition and stability,all of which are critical for disease progression.Conventional im...Objective Atherosclerosis involves not only the narrowing of blood vessels and plaque accumulation but also changes in plaque composition and stability,all of which are critical for disease progression.Conventional imaging techniques such as magnetic resonance angiography(MRA)and digital subtraction angiography(DSA)primarily assess luminal narrowing and plaque size,but have limited capability in identifying plaque instability and inflammation within the vascular muscle wall.This study aimed to develop and evaluate a novel imaging approach using ligand-modified nanomagnetic contrast(lmNMC)nanoprobes in combination with molecular magnetic resonance imaging(mMRI)to visualize and quantify vascular inflammation and plaque characteristics in a rabbit model of atherosclerosis.Methods A rabbit model of atherosclerosis was established and underwent mMRI before and after administration of lmNMC nanoprobes.Radiomic features were extracted from segmented images using discrete wavelet transform(DWT)to assess spatial frequency changes and gray-level co-occurrence matrix(GLCM)analysis to evaluate textural properties.Further radiomic analysis was performed using neural network-based regression and clustering,including the application of self-organizing maps(SOMs)to validate the consistency of radiomic pattern between training and testing data.Results Radiomic analysis revealed significant changes in spatial frequency between pre-and post-contrast images in both the horizontal and vertical directions.GLCM analysis showed an increase in contrast from 0.08463 to 0.1021 and a slight decrease in homogeneity from 0.9593 to 0.9540.Energy values declined from 0.2256 to 0.2019,while correlation increased marginally from 0.9659 to 0.9708.Neural network regression demonstrated strong convergence between target and output coordinates.Additionally,SOM clustering revealed consistent weight locations and neighbor distances across datasets,supporting the reliability of the radiomic validation.Conclusion The integration of lmNMC nanoprobes with mMRI enables detailed visualization of atherosclerotic plaques and surrounding vascular inflammation in a preclinical model.This method shows promise for enhancing the characterization of unstable plaques and may facilitate early detection of high-risk atherosclerotic lesions,potentially improving diagnostic and therapeutic strategies.展开更多
Atherosclerosis(AS)is a long-term vascular disorder primarily initiated by the combined effects of lipid deposition,endothelial injury,and inflammatory responses.It can even lead to death and represent a significant t...Atherosclerosis(AS)is a long-term vascular disorder primarily initiated by the combined effects of lipid deposition,endothelial injury,and inflammatory responses.It can even lead to death and represent a significant threat to human health and well-being.Lipophagy,a form of selective autophagy discovered recently,is defined as degrading lipid droplets through autophagic pathways to eliminate excess lipids.Studies have shown that lipophagy is critical in several key pathological processes of AS,including inflammation,oxidative stress damage,and foam cell formation.It is also closely associated with the instability of lipid plaques.This paper aims to provide an overview of recent domestic and international research on the characteristic mechanisms of lipophagy in the formation and progression of AS.It also summarizes the role of traditional Chinese medicine in regulating lipophagy to intervene in the progression of AS.The objective is to enhance the understanding of lipophagy and promote greater attention to the use of traditional Chinese medicine in preventing and managing AS.展开更多
OBJECTIVE:To investigate the effects of Huayu Qutan recipe(化瘀祛痰方,HYQT)on the atherosclerosis(AS)model of ApoE-/-mice with a high-fat diet and to illustrate the underlying mechanisms from modern pathophysiological...OBJECTIVE:To investigate the effects of Huayu Qutan recipe(化瘀祛痰方,HYQT)on the atherosclerosis(AS)model of ApoE-/-mice with a high-fat diet and to illustrate the underlying mechanisms from modern pathophysiological conceptualizations.METHODS:High performance liquid chromatography of quadrupole time of flight-tandem mass spectrometry(HPLC-Q-TOF-MS/MS)analysis was used to identify the active compounds in the recipe.The mice were randomly allocated into 7 groups:control(CTRL)group,normal diet(ND)group,high-fat diet(HFD)group,HYQT groups(low dose,medium dose,and high dose),and simvastatin(SIM)group.Deferent doses of HYQT were gavaged twice a day,and then the protective effect of HYQT on plaque formation in ApoE-/-mice with a high-fat diet was verified via hematoxylin-eosin(HE)staining and oil red o(ORO)staining.We observed the co-localization in aortic macrophages and lipid droplets(LDs)by CD68 and the Bodipy fluorescence probe.Light chain 3 phosphoprotein classⅡ/light chain 3 phosphoprotein classⅠ(LC3Ⅱ/LC3Ⅰ)was examined by western blotting,and sequestosome 1(SQSTM1/p62),Beclin1,Lamp1,mammalian target of rapamycin(mTOR),phosphorylated mammalian target of rapamycin(p-mTOR),and ATPbinding cassette transporter A1(ABCA1)were examined by real-time polymerase chain reaction(RT-PCR)and Western blotting.Transcription factor EB(TFEB)nuclear translocation was determined by immunofluorescence analysis.RESULTS:Five active compounds were identified using HPLC-Q-TOF-MS/MS analysis:ferulic acid,chlorogenic acid,calycosin,formononetin,and 8,2'-dihydroxy-7,4'-dimethoxy-isoflavane.The effect of HYQT on atherosclerotic plaque formation in Apo E-/-mice was investigated.These findings showed that HYQT decreased the co-localization of CD68 and Bodipy and increased the co-localization of CD68 and LC3B.Medium and high doses of HYQT increased autophagosome formation and promoted the maturation of LC3Ⅱ/LC3Ⅰ.Additionally,HYQT decreased the expression of SQSTM1/p62.Medium and high doses of HYQT also increased the expression of Beclin1 and Lamp1.RT-PCR and Western blot results suggested that HYQT enhanced the expression of ABCA1 mRNA and protein and regulated the mTORC1/TFEB signaling pathway.CONCLUSION:The results indicate that HYQT is an effective traditional Chinese herbal remedy for the treatment of AS.HYQT mitigates macrophage-derived foam cell formation by activating autophagy in atherosclerosis.The m TOR/TFEB signaling pathway and ABCA1 are therapeutic targets of HYQT for the treatment of AS.展开更多
BACKGROUND Serum retinol-binding protein(RBP)is the primary transport protein of circulating vitamin A.RBP has a crucial role in maintaining nutrient metabolism and physiologic homeostasis.Several studies have indicat...BACKGROUND Serum retinol-binding protein(RBP)is the primary transport protein of circulating vitamin A.RBP has a crucial role in maintaining nutrient metabolism and physiologic homeostasis.Several studies have indicated that serum RBP participates in the progression of diabetes and diabetes-related complications.However,the impact of serum RBP on lower limb atherosclerosis has not been determined in individuals with type 2 diabetes mellitus(T2DM).AIM To determine the association between serum RBP and lower limb atherosclerosis in individuals with T2DM.METHODS This retrospective study enrolled 4428 eligible T2DM patients and divided the patients into non-lower limb atherosclerosis(n=1913)and lower limb atherosclerosis groups(n=2515)based on lower limb arterial ultrasonography results.At hospital admission,baseline serum RBP levels were assessed,and all subjects were categorized into three groups(Q1-Q3)based on RBP tertiles.Logistic regression,restricted cubic spline regression,subgroup analysis,and machine learning were used to assess the association between RBP levels and lower limb atherosclerosis risk.RESULTS Among 4428 individuals with T2DM,2515(56.80%)had lower limb atherosclerosis.Logistic analysis showed that lower limb atherosclerosis risk increased by 1%for every 1 unit rise in serum RBP level(odds ratio=1.01,95%confidence interval:1.00-1.02,P=0.004).Patients in the highest tertile group(Q3)had a higher lower limb atherosclerosis risk compared to the lowest tertile group(Q1)(odds ratio=1.36,95%confidence interval:1.12-1.67,P=0.002).The lower limb atherosclerosis risk gradually increased with an increase in RBP tertile(P for trend=0.005).Restricted cubic spline analysis indicated a linear correlation between serum RBP levels and lower limb atherosclerosis risk(non-linear P<0.05).Machine learning demonstrated the significance and diagnostic value of serum RBP in predicting lower limb atherosclerosis risk.CONCLUSION Elevated serum RBP levels correlate with an increased lower limb atherosclerosis risk in individuals with T2DM.展开更多
BACKGROUND Carotid atherosclerosis is a complex disease involving multiple cellular and molecular pathways.Mesenchymal stem cells(MSCs)show therapeutic potential,but their optimal targets and efficacy are still under ...BACKGROUND Carotid atherosclerosis is a complex disease involving multiple cellular and molecular pathways.Mesenchymal stem cells(MSCs)show therapeutic potential,but their optimal targets and efficacy are still under study.MiR-126 enhances endothelial function and promotes angiogenesis by relieving vascular endothelial growth factor signaling suppression,suggesting its potential in vascular rege-neration.However,its role in directing stem cell differentiation toward endo-thelial lineages remains unclear.We hypothesize that miR-126 may influence MSCs’immunomodulatory and vascular reparative functions via the mitogen-activated protein kinases/extracellular signal-regulated kinase(MAPK/ERK)pathway,thereby improving carotid atherosclerosis.This study explores this mechanism to provide novel insights and support the development of miR-126-based therapeutic strategies.AIM To verify if miR-126 inhibits carotid atherosclerosis via the MAPK/ERK pathway.METHODS Rat bone marrow MSCs(product No.CP-R131,Wuhan,China)were verified by flow cytometry.The effects of miR-126 on MSCs’proliferation,migration,apoptosis,and cytokine expression were explored using microRNA mimics and inhibitors.Fluorescence staining quantified CD31+cells to evaluate endothelial differentiation.In vivo differentiation was assessed,and MSCs were transplanted into a rat carotid artery balloon dilatation model.Rats were randomly divided into five groups:Control,negative control mimics,miR-126 mimics,negative control inhibitor,and miR-126 inhibitor.RESULTS In vitro,MSCs treated with miR-126 mimics demonstrated enhanced proliferation,increased migration,and reduced apoptosis.These miR-126 mimics also significantly increased the secretion of vascular endothelial growth factor and basic fibroblast growth factor.Fluorescence and tissue staining indicated a higher proportion of CD31+cells in the miR-126 mimics group.Additionally,the expression of endothelial-related genes(von Willebrand factor,endothelial nitric oxide synthase,and vascular endothelial-cadherin)was upregulated in this group.In vivo,miR-126-transfected MSCs effectively reduced neointimal thickness and promoted endothelial coverage in rats.MiR-126 stimulated MSC proliferation in a dose-dependent manner and reduced p38 and ERK1/2 phosphorylation.Conversely,miR-126 inhibition or blank controls resulted in opposing effects.CONCLUSION MiR-126 exerts significant modulatory effects on the immunoregulatory and vascular reparative functions of MSCs through the MAPK/ERK signaling pathway,promoting their differentiation into endothelial cells and thereby mitigating atherosclerosis.展开更多
The CX3CL1/CX3CR1 signaling axis is established as a pivotal regulator in the pathogenesis of atherosclerosis,with well-documented roles in orchestrating inflammatory responses,mediating immune cell recruitment,and in...The CX3CL1/CX3CR1 signaling axis is established as a pivotal regulator in the pathogenesis of atherosclerosis,with well-documented roles in orchestrating inflammatory responses,mediating immune cell recruitment,and influencing vascular remodeling.This review provides a comprehensive synthesis of current knowledge regarding the structural characteristics and functional properties of the CX3CL1/CX3CR1 pathway.This study delves into its specific mechanistic contributions to atherosclerosis,placing particular emphasis on its regulatory influence across diverse cell types,including arterial endothelial cells,smooth muscle cells,and macrophages.Furthermore,the pathway’s integral involvement in both the initiation and progression of atherosclerotic plaques is dissected,highlighting its critical impact on plaque stability and susceptibility to rupture.The review also extends to the pathogenic significance of CX3CL1/CX3CR1 signaling in atherosclerosis-related comorbidities,incorporating the latest advancements in understanding its roles in coronary heart disease,stroke,and other cardiovascular disorders.By critically integrating findings from the extant literature,this review constructs a foundational framework to guide future investigations and underscores the substantial translational potential of targeting this pathway for therapeutic intervention in clinical settings.展开更多
Rosuvastatin (RVS) is an excellent drug with anti-inflammatory and lipid-lowering properties in the academic and medical fields. However, this drug faces a series of challenges when used to treat atherosclerosis cause...Rosuvastatin (RVS) is an excellent drug with anti-inflammatory and lipid-lowering properties in the academic and medical fields. However, this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia (HHcy), including high oral dosage, poor targeting, and long-term toxic side effects. In this study, we applied nanotechnology to construct a biomimetic nano-delivery system, macrophage membrane (Møm)-coated RVS-loaded Prussian blue (PB) nanoparticles (MPR NPs), for improving the bioavailability and targeting capacity of RVS, specifically to the plaque lesions associated with HHcy-induced atherosclerosis. In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4 (TLR4)/hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding and oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathways, reducing pyroptosis and inflammatory response in macrophages. Additionally, MPR NPs reversed the abnormal distribution of adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1)/ATP binding cassette transporter G1 (ABCA1)/ATP binding cassette transporter G1 (ABCG1) caused by HIF-1α, promoting cholesterol efflux and reducing lipid deposition. In vivo studies using apolipoprotein E knockout (ApoE^(−/−)) mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable biosecurity, and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes. These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.展开更多
The aim of this study was to explore the impact of chronic apical periodontitis(CAP)on atherosclerosis in apoE^(−/−)mice fed high-fat diet(HFD).This investigation focused on the gut microbiota,metabolites,and intestin...The aim of this study was to explore the impact of chronic apical periodontitis(CAP)on atherosclerosis in apoE^(−/−)mice fed high-fat diet(HFD).This investigation focused on the gut microbiota,metabolites,and intestinal barrier function to uncover potential links between oral health and cardiovascular disease(CVD).In this study,CAP was shown to exacerbate atherosclerosis in HFD-fed apoE^(−/−)mice,as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining.16S rRNA sequencing revealed significant alterations in the gut microbiota,with harmful bacterial species thriving while beneficial species declining.Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis,leading to elevated levels of taurochenodeoxycholic acid(TCDCA),taurocholic acid(TCA),and tauroursodeoxycholic acid(TDCA).These metabolic shifts may contribute to atherosclerosis development.Furthermore,impaired intestinal barrier function,characterized by reduced mucin expression and disrupted tight junction proteins,was observed.The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions,highlighting the importance of the intestinal barrier in cardiovascular health.In conclusion,this research underscores the intricate interplay among oral health,gut microbiota composition,metabolite profiles,and CVD incidence.These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues,as well as the need for further investigations into the intricate mechanisms linking oral health,gut microbiota,and metabolic pathways in CVD development.展开更多
OBJECTIVE:To investigate the effect of Taohong Siwu decoction(桃红四物汤,TSD)on atherosclerosis in rats as well as investigate the underlying mechanism based on molecular docking.METHODS:Sixty healthy male Sprague-Daw...OBJECTIVE:To investigate the effect of Taohong Siwu decoction(桃红四物汤,TSD)on atherosclerosis in rats as well as investigate the underlying mechanism based on molecular docking.METHODS:Sixty healthy male Sprague-Dawley rats were randomly divided into 6 groups with 10 rats in each group:control group,model group,atorvastatin group(AT,2.0 mg/kg),and TSD groups(20,10,5 g/kg)after 7 d of acclimation.The model of atherosclerosis was successfully established except the control group by high fat diet(HFD)and vitamin D2.Biochemical analyzers were used to detect the levels of triglyceride(TG),total cholestero(TC),low density lipoprotein-cholesterol(LDLC)and high density lipid-cholesterol(HDL-C)in blood lipid.The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1β)were determined by enzyme-linked immunosorbent assay.Sudan IV staining and Hematoxylin and eosin staining(HE staining)were performed to observe the pathological changes in aortic tissue.Molecular docking technology was used to predict the best matching between the main components of TSD and the target proteins.The expression of target proteins was further detected by quantitative real time polymerase chain reaction(q RTPCR)and Western blot analysis.RESULTS:The results showed that TSD restricted atherosclerosis development and decreased the inflammatory cytokines in plasma.Molecular docking results predicted that the main components of TSD showed a strong binding ability with toll-like receptor(TLR4),myeloid differentiation primary response protein 88(My D88),and nuclear factor kappa-B(NF-κB).The results of q RT-PCR and Western blot analysis showed that the m RNA and protein expressions of TLR4,My D88 and NF-κB p65 in the aorta were reduced in atorvastatin group and TSD group.CONCLUSIONS:TSD can ameliorate atherosclerosis in rats,and the underlying mechanism is supposed be related to the suppression of inflammatory response by regulating TLR4/My D88/NF-κB signal pathway.展开更多
Objective:To observe the effects of Danggui Shaoyao powder(DSP)on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor(PPARγ)-liver X receptor(LXRα)-aden...Objective:To observe the effects of Danggui Shaoyao powder(DSP)on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor(PPARγ)-liver X receptor(LXRα)-adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)pathway regulation.Methods: Eight C57BL/6J male mice were selected as the control group,and 24 ApoE^(−/−)male mice were randomly divided into the atherosclerosis model(AS)group,atorvastatin calcium(AC)group,and DSP group(n=8 each group).To establish an AS model,ApoE^(−/−)mice were fed a high-fat diet for 16 weeks.Pathologic changes in the aortic vasculature and liver were identified using Oil Red O staining.Triglyceride(TG),cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were determined in the livers using a single-reagent GPO-PAP method.Fluorescence quantitative polymerase chain reaction and western blot were used to observe and evaluate the mRNA and protein expression of the PPARγ-LXRα-ABCA1 intermediates in the liver.Results: After 16 weeks of a high-fat diet,ApoE^(−/−)mice showed more Oil Red O staining in the aorta and liver compared to the CONT group.Compared to the AS group,the DSP and AC treatment reduced aortic plaque and hepatic lipid deposition to varying degrees.Furthermore,DSP significantly reduced the hepatic lipid area in ApoE^(−/−)mice(P<.001)and decreased the levels of TG,TC,and LDL-C in liver(P<.001,P=.027,P<.001,respectively).DSP also significantly increased the levels of PPARγ,LXRα,ABCA1,and ABCG1 mRNA expression,as well as the PPARγ,LXRα,ABCA1,and ABCG1 protein expression in liver.Conclusion: DSP improved hepatic lipid metabolism via PPARγ-LXRα-ABCA1 pathway modulation for AS treatment.展开更多
Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disabili...Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.展开更多
Atherosclerosis(AS)is characterized by impairment and apoptosis of endothelial cells,continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells,which is documented as the traditional ce...Atherosclerosis(AS)is characterized by impairment and apoptosis of endothelial cells,continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells,which is documented as the traditional cellular paradigm.However,the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis,transdifferentiation and novel cell death forms such as ferroptosis,pyroptosis,and extracellular trap were reported.Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets.On the other side,the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS burden.Stem cell-or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects.Given the complexity of pathological changes of AS,attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging.In this review,the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical translation.The future challenges and improvements were also discussed.展开更多
Objective:Atherosclerotic cardiovascular disease poses a significant health challenge globally.Recent findings highlight the pivotal role of the endothelial-to-mesenchymal transition(End MT)in atherosclerosis.Morin is...Objective:Atherosclerotic cardiovascular disease poses a significant health challenge globally.Recent findings highlight the pivotal role of the endothelial-to-mesenchymal transition(End MT)in atherosclerosis.Morin is a bioflavonoid mainly extracted from white mulberry,a traditional Chinese herbal medicine with anti-inflammatory and antioxidant properties.This study examines whether morin can alleviate atherosclerosis by suppressing End MT and seeks to elucidate the underlying mechanism.Methods:We induced an in vitro End MT model in human umbilical vein endothelial cells(HUVECs)by stimulating the cells with transforming growth factor-β1(TGF-β1)(10 ng/m L)for 48 h.The in vivo experiments were performed in an atherosclerosis model using apolipoprotein E(Apo E)^(-/-)mice fed with a high-fat diet(HFD).Mice in the intervention group were given morin(50 mg/kg)orally for 4 weeks.Molecular docking and microscale thermophoresis were assayed to understand the interactions between morin and matrix metalloproteinase-9(MMP-9).Results:Morin inhibited the expression of End MT markers in a dose-dependent manner in TGF-β1-treated HUVECs.Administering 50μmol/L morin suppressed the upregulation of MMP-9 and Notch-1 signaling in TGF-β1-induced End MT.Moreover,the overexpression of MMP-9 activated Notch-1 signaling,thereby reversing morin's inhibitory effect on End MT.In the HFD-induced atherosclerotic Apo E^(-/-)mice,morin notably reduced aortic intimal hyperplasia and plaque formation by suppressing End MT.Furthermore,morin demonstrated a strong binding affinity for MMP-9.Conclusion:Morin acts as an MMP-9 inhibitor to disrupt End MT in atherosclerosis by limiting the activation of Notch-1 signaling.This study underscores morin's potential utility in the development of antiatherosclerotic medication.展开更多
Background:To explore potential biomarkers for early diagnosis of atherosclerosis(AS)and provide basic data for further research on AS,the characteristics of serum metabolomics during the progression of AS in mini-pig...Background:To explore potential biomarkers for early diagnosis of atherosclerosis(AS)and provide basic data for further research on AS,the characteristics of serum metabolomics during the progression of AS in mini-pigs were observed dynamically.Methods:An AS model in Bama miniature pigs was established by a high-cholesterol and high-fat diet.Fasting serum samples were collected monthly for metabolomics and serum lipid detection.At the end of the treatment period,pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS,thereby distinguishing the susceptibility of mini-pigs to AS.The metabolomics was de-tected using a high-resolution untargeted metabolomic approach.Statistical analysis was used to identify metabolites associated with AS susceptibility.Results:Based on pathological analysis,mini-pigs were divided into two groups:a susceptible group(n=3)and a non-susceptible group(n=6).A total of 1318 metabo-lites were identified,with significant shifting of metabolic profiles over time in both groups.Dynamic monitoring analysis highlighted 57 metabolites that exhibited an ob-vious trend of differential changes between two groups with the advance of time.The KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis in-dicated significant disorders in cholesterol metabolism,primary bile acid metabolism,histidine metabolism,as well as taurine and hypotaurine metabolism.Conclusions:During the progression of AS in mini-pigs induced by high-cholesterol/high-fat diet,the alterations in serum metabolic profile exhibited a time-dependent pattern,accompanied by notable disturbances in lipid metabolism,cholesterol me-tabolism,and amino acid metabolism.These metabolites may become potential bio-markers for early diagnosis of AS.展开更多
BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammato...BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.展开更多
基金funded by the National Natural Science Foundation of China,grant numbers 82374048 and 82174096Natural Science Foundation of Zhejiang Province,grant number LZ21H280001.
文摘Atherosclerosis(AS)is a progressive inflammatory disease,and thrombosis most likely leads to cardiovascular morbidity and mortality globally.Thrombolytic drugs alone cannot completely prevent thrombotic events,and treatments targeting thrombosis also need to regulate the inflammatory process.Based on the dynamic pathological development of AS,biomimetic thrombus-targeted nanoparticles HMTL@PM were prepared.Hirudin and lumbrukinase,effective substances of traditional Chinese medicine,were self-assembled under the action of tannic acid and Mn^(2+).HMTL@PM dissociated in the weakly acidic microenvironment of atherosclerosis and exhibited excellent therapeutic effects,including alleviating inflammation,dissolving thrombus,anticoagulation,and promoting cholesterol efflux.HMTL@PM effectively regulated the progression of AS and provided a newperspective for the development of drug delivery systems for AS therapy,which holds important research significance for reducing the mortality of cardiovascular and cerebrovascular diseases.
基金German Heart Foundation/German Foundation of Heart Research。
文摘Background:Aortic atherosclerosis increases the risk of embolic events under extracorporeal circulation(ECC).To evaluate the hemodynamic impact of ECC on atheromatous plaques,an atherosclerosis animal model,which is also eligible for ECC,is required.Methods:Twenty-nine New Zealand White rabbits received a pro-atherosclerotic diet(group diet,n=10),a pro-atherosclerotic diet and additional intraaortic balloon insufflation injury(group BI,n=9),or served as controls(n=10).After 3 or 6 months,aortic explants were analyzed by(immuno-)histology and RT-PCR.Results:Blood serum analyses revealed increased cholesterol-levels in groups diet and BI compared to controls(3 months:p=0.03 each,6 months:p<0.0001 each).Aortic inflammatory infiltration was significantly enhanced in groups diet(CD3 at 3 months:p<0.0001,6 months:p=0.02;CD68 at 3 months:p=0.01)and BI(CD3 at 3 months:p<0.0001,6 months:p=0.03;CD68 at 3 months:p=0.04,6 months:p=0.02).Increased intima hyperplasia occurred in both groups(p<0.0001 each).Macroscopic analyses after 3 and 6 months showed ubiquitous lumen-narrowing aortic plaques.Calcification of the intima and media was increased in groups diet(intima:p<0.0001 at 3 and 6 months;media at 3 months:p<0.0001,6 months:p=0.01)and BI(intima:p<0.0001 at 3 and 6 months;media at 3 months:p<0.0001,6 months:p=0.02).Extensive lipid accumulation was found in the intima in both treatment groups(p<0.0001 each).Conclusions:A rabbit model with high aortic calcific plaque burden—diet-induced with no implicit need of an additional intimal injury by an intraaortic balloon insufflation due to comparable outcome—exhibiting multiple pathophysiological aspects of human atherosclerosis has been designed and thoroughly characterized.It is suitable for use in future studies on the interaction between atherosclerotic plaques and the arterial blood flow under ECC.
基金supported by the National Natural Science Foundation of China(82374367)Jiangxi Provincial Natural Science Foundation(20242BAB26163,20232BAB206144)+4 种基金Jiangxi Province Key Laboratory of Traditional Chinese Medicine for Cardiovascular Diseases(20242BCC32096)NATCM’s Project of High-level Construction of Key TCM Disciplines(zyyzdxk-2023113)Project of Key Discipline Construction Fund of Jiangxi University of Chinese Medicine(2023jzzdxk032)Science and Technology Innovation Team Development Program of Jiangxi University of Chinese Medicine(CXTD22011)National Traditional Chinese Medicine Inheritance and Innovation Center Construction Project.
文摘Background:Atherosclerosis(AS),the primary pathological foundation of cardiovascular diseases,is characterized by intricate processes including inflammation,lipid metabolism disorders,and pyroptosis.While the traditional Chinese medicine compound Dingxin Recipe(DXR)has demonstrated definitive clinical efficacy in treating AS,its therapeutic mechanisms remain unclear.This study employed an integrated approach combining network pharmacology,molecular docking,and molecular dynamics simulations(MDS)to investigate DXR’s anti-AS mechanisms.Methods:Active ingredients and targets of DXR were identified and screened using databases such as GeneCards,OMIM,and TCMSP.An“ingredient-target-disease”network was constructed to visualize these interactions.Molecular docking was utilized to assess the binding affinity between key ingredients and their respective targets.Additionally,MDS were conducted to analyze the stability of these complexes,providing robust evidence for further clinical applications and in-depth research.Results:Through network pharmacology analysis,we identified 99 active drug components,934 gene targets,and 1463 disease targets associated with DXR.Protein-protein interaction analysis revealed central regulatory nodes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that these components primarily modulate processes such as inflammatory response and transcription factor activation,and are closely linked to the AGERAGE signaling pathway,lipid metabolism,and atherosclerosis pathways.Molecular docking confirmed strong binding potential between the components and their targets,while MDS further validated the stability of these interactions.Conclusion:This study elucidates that the active ingredients in DXR alleviate AS by mitigating inflammatory responses and inhibiting pyroptosis through the suppression of inflammatory factor release.These findings provide a scientific foundation for the clinical application of DXR in AS treatment.
基金supported by the National Key Research and Development Programme of China(No.2022YFF1100601)the National Natural Science Foundation of China(Nos.82321005,82373886,82173886 and 82404997)+3 种基金the Overseas Expertise Introduction Project for Discipline Innovation(No.G20582017001)the Project of State Key Laboratory of Natural Medicines,China Pharmaceutical University(No.SKLNMZZ202402)the CAMS Innovation Fund for Medical Sciences(No.2021-12M-5-011)the China Postdoctoral Science Foundation(No.2022M723514).
文摘The host-microbe co-metabolism system,generating diverse exogenous and endogenous bioactive molecules that influence the host’s immune and metabolic functions,plays a crucial role in the pathogenesis of atherosclerosis.Recent studies have elucidated the interaction between natural medicines and this co-metabolism system.Upon oral administration,natural medicine ingredients can undergo transformation by gut microbiota,potentially enhancing their bioavailability or anti-atherogenic efficacy.Furthermore,natural medicines can exert anti-atherogenic effects via modulation of endogenous host-microbe co-metabolism.This review presents an updated understanding of the dual association between natural medicines and host-microbe co-metabolites.It explores the critical function of microbial exogenous metabolites derived from natural medicines and uncovers the mechanisms underlying natural medicines’intervention on key nodes of endogenous host-microbe co-metabolism.These insights may offer new perspectives for cardiovascular disease(CVD)treatment and guide future drug discovery efforts.
基金the research funds from the National Natural Science Foundation of China(32272294)。
文摘Red wine has a good potential for alleviating atherosclerosis,but the mechanisms related to hepatointestinal circulation remain to be elucidated.This study showed that administration of a high-polyphenol red wine(16 mL/(kg·day))for 16 weeks significantly reduced the atherosclerotic lesion in high-fat diet-fed ApoE^(-/-)mice.The total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C)levels of plasma were lowered by 11.54%and 18.98%.The pro-inflammatory cytokines including interleukin-6(IL-6)and tumor necrosis factorα(TNF-α)levels were decreased by 27.59%and 31.92%.Red wine also reduced triglyceride(TG)level and lipid deposition in the liver,and increased the concentration of total bile acids(TBA).Untargeted metabolomics analysis indicated that red wine modulated the disorder of liver metabolism by regulating sphingolipid signaling pathway,sphingolipid metabolism,glycerophosphlipid metabolism,choline metabolism and bile secretion.16S rRNA sequencing revealed that red wine increased the abundance of Akkermansia and Bifidobacterium and reduced the abundance of Mucispirillum,Romboutsia,Lactobacillus,Bilophila and Blautia,along with the increased concentrations of short-chain fatty acids(SCFAs)in feces.These findings indicated that red wine could exert anti-atherosclerotic effect by regulating gut microbiota,restoring SCFAs,alleviating liver metabolic disorders.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF),funded by the Ministry of Education(Grant number:RS-2023-00248763).
文摘Objective Atherosclerosis involves not only the narrowing of blood vessels and plaque accumulation but also changes in plaque composition and stability,all of which are critical for disease progression.Conventional imaging techniques such as magnetic resonance angiography(MRA)and digital subtraction angiography(DSA)primarily assess luminal narrowing and plaque size,but have limited capability in identifying plaque instability and inflammation within the vascular muscle wall.This study aimed to develop and evaluate a novel imaging approach using ligand-modified nanomagnetic contrast(lmNMC)nanoprobes in combination with molecular magnetic resonance imaging(mMRI)to visualize and quantify vascular inflammation and plaque characteristics in a rabbit model of atherosclerosis.Methods A rabbit model of atherosclerosis was established and underwent mMRI before and after administration of lmNMC nanoprobes.Radiomic features were extracted from segmented images using discrete wavelet transform(DWT)to assess spatial frequency changes and gray-level co-occurrence matrix(GLCM)analysis to evaluate textural properties.Further radiomic analysis was performed using neural network-based regression and clustering,including the application of self-organizing maps(SOMs)to validate the consistency of radiomic pattern between training and testing data.Results Radiomic analysis revealed significant changes in spatial frequency between pre-and post-contrast images in both the horizontal and vertical directions.GLCM analysis showed an increase in contrast from 0.08463 to 0.1021 and a slight decrease in homogeneity from 0.9593 to 0.9540.Energy values declined from 0.2256 to 0.2019,while correlation increased marginally from 0.9659 to 0.9708.Neural network regression demonstrated strong convergence between target and output coordinates.Additionally,SOM clustering revealed consistent weight locations and neighbor distances across datasets,supporting the reliability of the radiomic validation.Conclusion The integration of lmNMC nanoprobes with mMRI enables detailed visualization of atherosclerotic plaques and surrounding vascular inflammation in a preclinical model.This method shows promise for enhancing the characterization of unstable plaques and may facilitate early detection of high-risk atherosclerotic lesions,potentially improving diagnostic and therapeutic strategies.
基金supported by the National Nature Science Foundation of China(82374367)Jiangxi Provincial Natural Science Foundation(20242BAB26163,20232BAB206144)+3 种基金NATCM’s Project of High-level Construction of Key TCM Disciplines(zyyzdxk-2023113)Project of Key Discipline Construction Fund of Jiangxi University of Chinese Medicine(2023jzzdxk032)Science and Technology Innovation Team Development Program of Jiangxi University of Chinese Medicine(CXTD22011)Graduate Innovation Special Fund of Jiangxi University of Chinese Medicine(XJ-S202452).
文摘Atherosclerosis(AS)is a long-term vascular disorder primarily initiated by the combined effects of lipid deposition,endothelial injury,and inflammatory responses.It can even lead to death and represent a significant threat to human health and well-being.Lipophagy,a form of selective autophagy discovered recently,is defined as degrading lipid droplets through autophagic pathways to eliminate excess lipids.Studies have shown that lipophagy is critical in several key pathological processes of AS,including inflammation,oxidative stress damage,and foam cell formation.It is also closely associated with the instability of lipid plaques.This paper aims to provide an overview of recent domestic and international research on the characteristic mechanisms of lipophagy in the formation and progression of AS.It also summarizes the role of traditional Chinese medicine in regulating lipophagy to intervene in the progression of AS.The objective is to enhance the understanding of lipophagy and promote greater attention to the use of traditional Chinese medicine in preventing and managing AS.
基金the Science and Technology Research Project of Education Department of Liaoning Province:the Mechanism of Regulating Lipophagy and Affecting Cholesterol Efflux in Human Promyelocytic Leukemia Cell Line Macrophages by Huayu Qutan Recipe based on the Theory of"Laoxia Shengtan"(No.L202048)Youth Project of Basic Scientific Research Project of Education Department of Liaoning Province:Mechanism of Mitochondrial Autophagy and Apoptosis in L02 Hepatocytes Regulated by miR-7043-3p based on the Theory of"Spleen Qi Dispersing Essence"of Huayu Qutan Recipe(No.LJKQZ2021064)。
文摘OBJECTIVE:To investigate the effects of Huayu Qutan recipe(化瘀祛痰方,HYQT)on the atherosclerosis(AS)model of ApoE-/-mice with a high-fat diet and to illustrate the underlying mechanisms from modern pathophysiological conceptualizations.METHODS:High performance liquid chromatography of quadrupole time of flight-tandem mass spectrometry(HPLC-Q-TOF-MS/MS)analysis was used to identify the active compounds in the recipe.The mice were randomly allocated into 7 groups:control(CTRL)group,normal diet(ND)group,high-fat diet(HFD)group,HYQT groups(low dose,medium dose,and high dose),and simvastatin(SIM)group.Deferent doses of HYQT were gavaged twice a day,and then the protective effect of HYQT on plaque formation in ApoE-/-mice with a high-fat diet was verified via hematoxylin-eosin(HE)staining and oil red o(ORO)staining.We observed the co-localization in aortic macrophages and lipid droplets(LDs)by CD68 and the Bodipy fluorescence probe.Light chain 3 phosphoprotein classⅡ/light chain 3 phosphoprotein classⅠ(LC3Ⅱ/LC3Ⅰ)was examined by western blotting,and sequestosome 1(SQSTM1/p62),Beclin1,Lamp1,mammalian target of rapamycin(mTOR),phosphorylated mammalian target of rapamycin(p-mTOR),and ATPbinding cassette transporter A1(ABCA1)were examined by real-time polymerase chain reaction(RT-PCR)and Western blotting.Transcription factor EB(TFEB)nuclear translocation was determined by immunofluorescence analysis.RESULTS:Five active compounds were identified using HPLC-Q-TOF-MS/MS analysis:ferulic acid,chlorogenic acid,calycosin,formononetin,and 8,2'-dihydroxy-7,4'-dimethoxy-isoflavane.The effect of HYQT on atherosclerotic plaque formation in Apo E-/-mice was investigated.These findings showed that HYQT decreased the co-localization of CD68 and Bodipy and increased the co-localization of CD68 and LC3B.Medium and high doses of HYQT increased autophagosome formation and promoted the maturation of LC3Ⅱ/LC3Ⅰ.Additionally,HYQT decreased the expression of SQSTM1/p62.Medium and high doses of HYQT also increased the expression of Beclin1 and Lamp1.RT-PCR and Western blot results suggested that HYQT enhanced the expression of ABCA1 mRNA and protein and regulated the mTORC1/TFEB signaling pathway.CONCLUSION:The results indicate that HYQT is an effective traditional Chinese herbal remedy for the treatment of AS.HYQT mitigates macrophage-derived foam cell formation by activating autophagy in atherosclerosis.The m TOR/TFEB signaling pathway and ABCA1 are therapeutic targets of HYQT for the treatment of AS.
基金The study was approved by the ethics committee of Southwest Hospital,the First Affiliated Hospital of Army Medical University of Chinese People's Liberation Army(No.KY2024007).
文摘BACKGROUND Serum retinol-binding protein(RBP)is the primary transport protein of circulating vitamin A.RBP has a crucial role in maintaining nutrient metabolism and physiologic homeostasis.Several studies have indicated that serum RBP participates in the progression of diabetes and diabetes-related complications.However,the impact of serum RBP on lower limb atherosclerosis has not been determined in individuals with type 2 diabetes mellitus(T2DM).AIM To determine the association between serum RBP and lower limb atherosclerosis in individuals with T2DM.METHODS This retrospective study enrolled 4428 eligible T2DM patients and divided the patients into non-lower limb atherosclerosis(n=1913)and lower limb atherosclerosis groups(n=2515)based on lower limb arterial ultrasonography results.At hospital admission,baseline serum RBP levels were assessed,and all subjects were categorized into three groups(Q1-Q3)based on RBP tertiles.Logistic regression,restricted cubic spline regression,subgroup analysis,and machine learning were used to assess the association between RBP levels and lower limb atherosclerosis risk.RESULTS Among 4428 individuals with T2DM,2515(56.80%)had lower limb atherosclerosis.Logistic analysis showed that lower limb atherosclerosis risk increased by 1%for every 1 unit rise in serum RBP level(odds ratio=1.01,95%confidence interval:1.00-1.02,P=0.004).Patients in the highest tertile group(Q3)had a higher lower limb atherosclerosis risk compared to the lowest tertile group(Q1)(odds ratio=1.36,95%confidence interval:1.12-1.67,P=0.002).The lower limb atherosclerosis risk gradually increased with an increase in RBP tertile(P for trend=0.005).Restricted cubic spline analysis indicated a linear correlation between serum RBP levels and lower limb atherosclerosis risk(non-linear P<0.05).Machine learning demonstrated the significance and diagnostic value of serum RBP in predicting lower limb atherosclerosis risk.CONCLUSION Elevated serum RBP levels correlate with an increased lower limb atherosclerosis risk in individuals with T2DM.
基金Supported by Hangzhou Bio-Medicine and Health Industry Development Support Science and Technology Project,No.2022WJC005,No.2024WJC105.
文摘BACKGROUND Carotid atherosclerosis is a complex disease involving multiple cellular and molecular pathways.Mesenchymal stem cells(MSCs)show therapeutic potential,but their optimal targets and efficacy are still under study.MiR-126 enhances endothelial function and promotes angiogenesis by relieving vascular endothelial growth factor signaling suppression,suggesting its potential in vascular rege-neration.However,its role in directing stem cell differentiation toward endo-thelial lineages remains unclear.We hypothesize that miR-126 may influence MSCs’immunomodulatory and vascular reparative functions via the mitogen-activated protein kinases/extracellular signal-regulated kinase(MAPK/ERK)pathway,thereby improving carotid atherosclerosis.This study explores this mechanism to provide novel insights and support the development of miR-126-based therapeutic strategies.AIM To verify if miR-126 inhibits carotid atherosclerosis via the MAPK/ERK pathway.METHODS Rat bone marrow MSCs(product No.CP-R131,Wuhan,China)were verified by flow cytometry.The effects of miR-126 on MSCs’proliferation,migration,apoptosis,and cytokine expression were explored using microRNA mimics and inhibitors.Fluorescence staining quantified CD31+cells to evaluate endothelial differentiation.In vivo differentiation was assessed,and MSCs were transplanted into a rat carotid artery balloon dilatation model.Rats were randomly divided into five groups:Control,negative control mimics,miR-126 mimics,negative control inhibitor,and miR-126 inhibitor.RESULTS In vitro,MSCs treated with miR-126 mimics demonstrated enhanced proliferation,increased migration,and reduced apoptosis.These miR-126 mimics also significantly increased the secretion of vascular endothelial growth factor and basic fibroblast growth factor.Fluorescence and tissue staining indicated a higher proportion of CD31+cells in the miR-126 mimics group.Additionally,the expression of endothelial-related genes(von Willebrand factor,endothelial nitric oxide synthase,and vascular endothelial-cadherin)was upregulated in this group.In vivo,miR-126-transfected MSCs effectively reduced neointimal thickness and promoted endothelial coverage in rats.MiR-126 stimulated MSC proliferation in a dose-dependent manner and reduced p38 and ERK1/2 phosphorylation.Conversely,miR-126 inhibition or blank controls resulted in opposing effects.CONCLUSION MiR-126 exerts significant modulatory effects on the immunoregulatory and vascular reparative functions of MSCs through the MAPK/ERK signaling pathway,promoting their differentiation into endothelial cells and thereby mitigating atherosclerosis.
基金Study on the Protective Mechanism of Safflower Yellow Pigment on Vascular Endothelial Function in Patients with Phlegm-Stasis Syndrome Coronary Heart Disease and Stable Angina Pectoris(Project No.20222A010012)Single-Cell Immune Panorama Study on Neiguan(PC6)Acupoint Injection for Improving Pyroptosis in Chronic Heart Failure(Project No.2025A03J3499)+1 种基金The study on the effect and mechanism of Guanxinning Tablets on vascular homeostasis and remodeling in populations with early vascular aging(Project No.2024QC-B1007)Guangzhou Key Laboratory of Traditional Chinese Medicine Rehabilitation(Project No.2024A03J0790).
文摘The CX3CL1/CX3CR1 signaling axis is established as a pivotal regulator in the pathogenesis of atherosclerosis,with well-documented roles in orchestrating inflammatory responses,mediating immune cell recruitment,and influencing vascular remodeling.This review provides a comprehensive synthesis of current knowledge regarding the structural characteristics and functional properties of the CX3CL1/CX3CR1 pathway.This study delves into its specific mechanistic contributions to atherosclerosis,placing particular emphasis on its regulatory influence across diverse cell types,including arterial endothelial cells,smooth muscle cells,and macrophages.Furthermore,the pathway’s integral involvement in both the initiation and progression of atherosclerotic plaques is dissected,highlighting its critical impact on plaque stability and susceptibility to rupture.The review also extends to the pathogenic significance of CX3CL1/CX3CR1 signaling in atherosclerosis-related comorbidities,incorporating the latest advancements in understanding its roles in coronary heart disease,stroke,and other cardiovascular disorders.By critically integrating findings from the extant literature,this review constructs a foundational framework to guide future investigations and underscores the substantial translational potential of targeting this pathway for therapeutic intervention in clinical settings.
基金supported by the National Natural Science Foundation of China(Grant Nos.:U21A20343,82160088,81870225,81870332,81700404,82271626,and 82260088)the Natural Science Foundation of Ningxia Autonomous Region,China(Grant Nos.:2020AAC02021,2020AAC02038,and 2022AAC05025)+5 种基金the Key Research and Development Projects in Ningxia Autonomous Region,China(Grant Nos.:2020BFH02003,2021BEG02033,2020BEG03008,and 2022BFH02013)the Basic Scientific Research Operating Expenses from the Public Welfare Research Institutes at the Central Level of the Chinese Academy of Medical Sciences,China(Grant No.:2019PT330002)the Ningxia Science and Technology Leading Talent Project,China(Grant No.:KJT2017007)the Natural Science Foundation of Hunan Province,China(Grant No.:2022JJ40698)the School-level Special Talent Launching Project of Ningxia Medical University,China(Grant No.:XT2018015)the Open Bidding for Selecting the Best Candidates Program of Ningxia Medical University,China(Grant No.:XJKF230106).
文摘Rosuvastatin (RVS) is an excellent drug with anti-inflammatory and lipid-lowering properties in the academic and medical fields. However, this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia (HHcy), including high oral dosage, poor targeting, and long-term toxic side effects. In this study, we applied nanotechnology to construct a biomimetic nano-delivery system, macrophage membrane (Møm)-coated RVS-loaded Prussian blue (PB) nanoparticles (MPR NPs), for improving the bioavailability and targeting capacity of RVS, specifically to the plaque lesions associated with HHcy-induced atherosclerosis. In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4 (TLR4)/hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding and oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathways, reducing pyroptosis and inflammatory response in macrophages. Additionally, MPR NPs reversed the abnormal distribution of adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1)/ATP binding cassette transporter G1 (ABCA1)/ATP binding cassette transporter G1 (ABCG1) caused by HIF-1α, promoting cholesterol efflux and reducing lipid deposition. In vivo studies using apolipoprotein E knockout (ApoE^(−/−)) mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable biosecurity, and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes. These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.
基金supported by the National Natural Science Foundation of China(No.81970926)supported by the Fujian Province Natural Science Foundation of China(No.2023J01709)the Fujian Provincial Health Technology Project(No.2022QNA073).
文摘The aim of this study was to explore the impact of chronic apical periodontitis(CAP)on atherosclerosis in apoE^(−/−)mice fed high-fat diet(HFD).This investigation focused on the gut microbiota,metabolites,and intestinal barrier function to uncover potential links between oral health and cardiovascular disease(CVD).In this study,CAP was shown to exacerbate atherosclerosis in HFD-fed apoE^(−/−)mice,as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining.16S rRNA sequencing revealed significant alterations in the gut microbiota,with harmful bacterial species thriving while beneficial species declining.Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis,leading to elevated levels of taurochenodeoxycholic acid(TCDCA),taurocholic acid(TCA),and tauroursodeoxycholic acid(TDCA).These metabolic shifts may contribute to atherosclerosis development.Furthermore,impaired intestinal barrier function,characterized by reduced mucin expression and disrupted tight junction proteins,was observed.The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions,highlighting the importance of the intestinal barrier in cardiovascular health.In conclusion,this research underscores the intricate interplay among oral health,gut microbiota composition,metabolite profiles,and CVD incidence.These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues,as well as the need for further investigations into the intricate mechanisms linking oral health,gut microbiota,and metabolic pathways in CVD development.
基金Supported by the National Natural Science Foundation of China:Investigating the Mechanism of Total Saponins in Treating Gouty Arthritis Based on Toll-like Receptor/Myeloid Differentiation Factor 88/Nuclear Factor-Kappa B Signal Pathway and Nacht Leucine-Rich Repeat Protein 3-Inflammasome(No.81573670)Study on the Material Basis and Pathway of Taohong Siwu Decoction in Regulating the Release of Platelet Alpha Granules in Postpartum Blood Stasis(No.81473387)+2 种基金Study on the Regulatory Mechanism of Taohong Siwu Decoction on Experimental Cerebral Ischemia Angiogenesis Based on the Messenger Effect of Platelet Microparticles(No.81503291)Investigating the Material Basis and Molecular Mechanism of Taohong Siwu Decoction Against Vascular Dementia Based on Microdialysis Technology and NOD-Like Receptor Protein 3 Inflammasome Vascular Endothelial Cell Interaction(No.81903953)the Anhui Province Key Research and Development Program:Research on the Development and Preparation of Taohong Siwu Granules(No.1704a0802141)。
文摘OBJECTIVE:To investigate the effect of Taohong Siwu decoction(桃红四物汤,TSD)on atherosclerosis in rats as well as investigate the underlying mechanism based on molecular docking.METHODS:Sixty healthy male Sprague-Dawley rats were randomly divided into 6 groups with 10 rats in each group:control group,model group,atorvastatin group(AT,2.0 mg/kg),and TSD groups(20,10,5 g/kg)after 7 d of acclimation.The model of atherosclerosis was successfully established except the control group by high fat diet(HFD)and vitamin D2.Biochemical analyzers were used to detect the levels of triglyceride(TG),total cholestero(TC),low density lipoprotein-cholesterol(LDLC)and high density lipid-cholesterol(HDL-C)in blood lipid.The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1β)were determined by enzyme-linked immunosorbent assay.Sudan IV staining and Hematoxylin and eosin staining(HE staining)were performed to observe the pathological changes in aortic tissue.Molecular docking technology was used to predict the best matching between the main components of TSD and the target proteins.The expression of target proteins was further detected by quantitative real time polymerase chain reaction(q RTPCR)and Western blot analysis.RESULTS:The results showed that TSD restricted atherosclerosis development and decreased the inflammatory cytokines in plasma.Molecular docking results predicted that the main components of TSD showed a strong binding ability with toll-like receptor(TLR4),myeloid differentiation primary response protein 88(My D88),and nuclear factor kappa-B(NF-κB).The results of q RT-PCR and Western blot analysis showed that the m RNA and protein expressions of TLR4,My D88 and NF-κB p65 in the aorta were reduced in atorvastatin group and TSD group.CONCLUSIONS:TSD can ameliorate atherosclerosis in rats,and the underlying mechanism is supposed be related to the suppression of inflammatory response by regulating TLR4/My D88/NF-κB signal pathway.
基金supported by the National Natural Science Foundation of China(82074325).
文摘Objective:To observe the effects of Danggui Shaoyao powder(DSP)on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor(PPARγ)-liver X receptor(LXRα)-adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)pathway regulation.Methods: Eight C57BL/6J male mice were selected as the control group,and 24 ApoE^(−/−)male mice were randomly divided into the atherosclerosis model(AS)group,atorvastatin calcium(AC)group,and DSP group(n=8 each group).To establish an AS model,ApoE^(−/−)mice were fed a high-fat diet for 16 weeks.Pathologic changes in the aortic vasculature and liver were identified using Oil Red O staining.Triglyceride(TG),cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were determined in the livers using a single-reagent GPO-PAP method.Fluorescence quantitative polymerase chain reaction and western blot were used to observe and evaluate the mRNA and protein expression of the PPARγ-LXRα-ABCA1 intermediates in the liver.Results: After 16 weeks of a high-fat diet,ApoE^(−/−)mice showed more Oil Red O staining in the aorta and liver compared to the CONT group.Compared to the AS group,the DSP and AC treatment reduced aortic plaque and hepatic lipid deposition to varying degrees.Furthermore,DSP significantly reduced the hepatic lipid area in ApoE^(−/−)mice(P<.001)and decreased the levels of TG,TC,and LDL-C in liver(P<.001,P=.027,P<.001,respectively).DSP also significantly increased the levels of PPARγ,LXRα,ABCA1,and ABCG1 mRNA expression,as well as the PPARγ,LXRα,ABCA1,and ABCG1 protein expression in liver.Conclusion: DSP improved hepatic lipid metabolism via PPARγ-LXRα-ABCA1 pathway modulation for AS treatment.
基金support from the Natural Science Foundation of Henan,China(Grant No.:202300410446)the National Natural Science Foundation of China(Grant No.:82071950).
文摘Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.
基金supported by the National Natural Science Foundation of China(No.81573957,No.81874461 and No.82070307).
文摘Atherosclerosis(AS)is characterized by impairment and apoptosis of endothelial cells,continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells,which is documented as the traditional cellular paradigm.However,the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis,transdifferentiation and novel cell death forms such as ferroptosis,pyroptosis,and extracellular trap were reported.Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets.On the other side,the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS burden.Stem cell-or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects.Given the complexity of pathological changes of AS,attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging.In this review,the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical translation.The future challenges and improvements were also discussed.
基金supported by grants from the National Key R&D Program of China(No.2019YFA0210100)the Young Scholars Fostering Fund of the First Affiliated Hospital of Nanjing Medical University(No.PY2022010[NP22])。
文摘Objective:Atherosclerotic cardiovascular disease poses a significant health challenge globally.Recent findings highlight the pivotal role of the endothelial-to-mesenchymal transition(End MT)in atherosclerosis.Morin is a bioflavonoid mainly extracted from white mulberry,a traditional Chinese herbal medicine with anti-inflammatory and antioxidant properties.This study examines whether morin can alleviate atherosclerosis by suppressing End MT and seeks to elucidate the underlying mechanism.Methods:We induced an in vitro End MT model in human umbilical vein endothelial cells(HUVECs)by stimulating the cells with transforming growth factor-β1(TGF-β1)(10 ng/m L)for 48 h.The in vivo experiments were performed in an atherosclerosis model using apolipoprotein E(Apo E)^(-/-)mice fed with a high-fat diet(HFD).Mice in the intervention group were given morin(50 mg/kg)orally for 4 weeks.Molecular docking and microscale thermophoresis were assayed to understand the interactions between morin and matrix metalloproteinase-9(MMP-9).Results:Morin inhibited the expression of End MT markers in a dose-dependent manner in TGF-β1-treated HUVECs.Administering 50μmol/L morin suppressed the upregulation of MMP-9 and Notch-1 signaling in TGF-β1-induced End MT.Moreover,the overexpression of MMP-9 activated Notch-1 signaling,thereby reversing morin's inhibitory effect on End MT.In the HFD-induced atherosclerotic Apo E^(-/-)mice,morin notably reduced aortic intimal hyperplasia and plaque formation by suppressing End MT.Furthermore,morin demonstrated a strong binding affinity for MMP-9.Conclusion:Morin acts as an MMP-9 inhibitor to disrupt End MT in atherosclerosis by limiting the activation of Notch-1 signaling.This study underscores morin's potential utility in the development of antiatherosclerotic medication.
基金Special Scientific Research Project of Laboratory Animals,Grant/Award Number:SYDW[2018]14,SYDW[2020]01 and SYDW-KY[2021]03。
文摘Background:To explore potential biomarkers for early diagnosis of atherosclerosis(AS)and provide basic data for further research on AS,the characteristics of serum metabolomics during the progression of AS in mini-pigs were observed dynamically.Methods:An AS model in Bama miniature pigs was established by a high-cholesterol and high-fat diet.Fasting serum samples were collected monthly for metabolomics and serum lipid detection.At the end of the treatment period,pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS,thereby distinguishing the susceptibility of mini-pigs to AS.The metabolomics was de-tected using a high-resolution untargeted metabolomic approach.Statistical analysis was used to identify metabolites associated with AS susceptibility.Results:Based on pathological analysis,mini-pigs were divided into two groups:a susceptible group(n=3)and a non-susceptible group(n=6).A total of 1318 metabo-lites were identified,with significant shifting of metabolic profiles over time in both groups.Dynamic monitoring analysis highlighted 57 metabolites that exhibited an ob-vious trend of differential changes between two groups with the advance of time.The KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis in-dicated significant disorders in cholesterol metabolism,primary bile acid metabolism,histidine metabolism,as well as taurine and hypotaurine metabolism.Conclusions:During the progression of AS in mini-pigs induced by high-cholesterol/high-fat diet,the alterations in serum metabolic profile exhibited a time-dependent pattern,accompanied by notable disturbances in lipid metabolism,cholesterol me-tabolism,and amino acid metabolism.These metabolites may become potential bio-markers for early diagnosis of AS.
文摘BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.
