BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the commo...BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the common comorbidities associated with DMA but is often refractory to current treatments.AIM To investigate the therapeutic effect of human amniotic fluid stem cell-derived extracellular vesicles(hAFSC-EVs)on the recovery of bladder dysfunction in DMA rats.METHODS Eighty rats were divided into normal control,streptozotocin-induced diabetic rats,diabetic rats subjected to arterial balloon endothelial injury of common iliac artery(DMA),and DMA rats treated with hAFSC-EVs(DMA+hAFSC-EVs).At 4 weeks and 12 weeks after DMA induction,levels of blood glucose,total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,homeostasis model assessment(HOMA)-insulin resistance,and HOMA-βwere measured.Cystometry,common iliac artery wall thickness,and bladder tumor necrosis factor(TNF)-α,interleukin(IL)-6,transforming growth factor(TGF)-β1,Smad3,connective tissue growth factor(CTGF)and fibronectin were also evaluated.RESULTS Bladder weight and blood glucose,triglyceride,HOMA-insulin resistance,common iliac artery intima thickness,voided volume,intercontraction interval,bladder capacity,and mRNA expression of TNF-α,IL-6,TGF-β1,Smad3,CTGF and fibronectin were significantly increased at 4 weeks and 12 weeks after induction,while the HOMA-βlevel decreased at 4 weeks and 12 weeks,and the high-density lipoprotein cholesterol level decreased at 12 weeks.hAFSC-EVs treatment in DMA rats significantly reduced bladder weight and blood glucose,thickness of common iliac arterial intima,voided volume,intercontraction interval and bladder capacity at 4 weeks.The mRNA expression of TNF-α,TGF-β1,and CTGF in DMA rats treated with hAFSC-EVs were significantly decreased at 4 weeks,while the mRNA expressions of IL-6 and Smad3 were significantly decreased 12 weeks.CONCLUSION hAFSC-EVs treatment can help restore DMA-induced bladder dysfunction,which is associated with lowered blood glucose levels,reduced arterial wall thickness,and decreased TNF-α,IL-6,TGF-β1,Smad3,and CTGF expression.展开更多
Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and tr...Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and treated with OA,and the levels of cell proliferation,migration,adhesion,and apoptosis were evaluated by BrdU staining,scratch healing assay,monocyte-endothelial cell adhesion assay and flow cytometry.The mice were fed with a high-fat diet to induce an atherosclerosis model,and treated with OA by gastric gavage.The mice were divided into the control group,the model group,and the OA administration group.The blood lipid and plaque formation in mice were detected.In addition,oxidative stress and mitochondrial structure and function changes in cells and mice were evaluated by transmission electron microscopy,JC-1 fluorescent probe,and Western blotting assays.The expression levels of proteins in the AMPK/Drp1 pathway were examined through Western blot.Results:OA markedly increased cell viability and migration rate of HUVECs,and decreased the adhesion rate of THP-1 cells and the apoptosis rate.OA significantly reduced serum lipid levels,such as total cholesterol and triglyceride,in mice and inhibited plaque formation in the aorta.OA also significantly increased the content of superoxide dismutase and catalase,alleviated mitochondrial damage,such as mitochondrial swelling and mitochondrial cristae reduction,reduced the number of mitochondria,increased adenosine triphosphate content,and significantly reduced p-Drp1(Ser616)/Drp1,MFF and FIS1 levels,increased p-AMPK/AMPK levels,activated AMPK,and then regulated DRP1 activity.Conclusions:OA activates AMPK,which in turn regulates the activity of DRP1 to restore normal mitochondrial dynamics and reduce atherosclerosis.展开更多
Objective:To investigate the anti-atherosclerosis effect of chikusetsusaponinⅣ(CSⅣ)against high-fat diet-induced atherosclerosis in rats.Methods:A high-fat diet was used for the induction of atherosclerosis in rats,...Objective:To investigate the anti-atherosclerosis effect of chikusetsusaponinⅣ(CSⅣ)against high-fat diet-induced atherosclerosis in rats.Methods:A high-fat diet was used for the induction of atherosclerosis in rats,and the rats received oral CSⅣor atorvastatin.The body weight,organ weights,food intake,calorie intake,lipid parameters,3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA)/mevalonate ratio,collagen,free fatty acid,cardiac parameters,apolipoprotein(A and B),antioxidant parameters,inflammatory cytokines,and inflammatory parameters were assessed.The mRNA expressions of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),IL-6,IL-17,PI3K,AKT,and mTOR were estimated.Results:CSⅣsignificantly modulated food intake,body weight,organ weight(liver,kidney,and heart),and calories(P<0.05).Total cholesterol,triglycerides,very low-density lipoprotein cholesterol,low-density lipoprotein cholesterol,cardiovascular risk index-1,and cardiovascular risk index-2 were decreased,while high-density lipoprotein cholesterol and anti-atherogenic index were increased significantly in the CSⅣgroup(P<0.05).Besides,CSⅣsignificantly restored the level of HMG-CoA/mevalonate ratio,collagen,free fatty acid,cardiac parameters(creatinine kinase-MB,lactate dehydrogenase,cTnT,cTnI),apolipoprotein(apolipoprotein A and apolipoprotein B),antioxidant parameters(MDA,CAT,GPx,GSH,SOD),inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-10),inflammatory parameters(COX-2,TGF-β,NF-κB),intercellular adhesion molecule-1,vascular cell adhesion molecule-1,and monocyte chemoattractant protein-1.CSⅣalso decreased the mRNA expression of IL-1β,TNF-α,IL-6,IL-17,PI3K,AKT,and mTOR.Conclusions:This study showed the anti-atherosclerosis effect of CSⅣagainst high-fat diet-induced atherosclerosis in rats via alteration of NF-κB/COX-2 and PI3K/AKT/mTOR signaling pathway.展开更多
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
Background In recent years,the incidence of coronary heart disease(CHD)has continued to rise,and its comorbidity with hyperlipidemia significantly increases the mortality risk in patients.Statin monotherapy faces limi...Background In recent years,the incidence of coronary heart disease(CHD)has continued to rise,and its comorbidity with hyperlipidemia significantly increases the mortality risk in patients.Statin monotherapy faces limitations in efficacy for some patients and raises potential safety concerns.Ezetimibe,as a novel lipid-modulating agent,exhibits potential advantages in the treatment of hyperlipidemia.Based on this,the present study investigated the therapeutic efficacy of ezetimibe in CHD patients with hyperlipidemia,as well as its effects on lipid metabolism and the amelioration of atherosclerosis.Methods In this study,150 clinical cases with CHD and hyperlipidemia admitted in our hospital from July 2022 to July 2024 were collected for retrospective analysis.According to different treatment methods,they were randomly divided into the Atorvastatin group(control group,n=75)and the Atorvastatin+Ezetimibe group(experimental group,n=75).Control group received atorvastatin monotherapy,while experimental group were administered additional ezetimibe as an adjunct to the atorvastatin-based treatment regimen.The clinical efficacy of the two treatment groups was analyzed,including cardiac function-related parameters such as the cardiac index(CI),cardiac output(CO),left ventricular ejection fraction(LVEF)and left ventricular end-diastolic diameter(LVEDD)before and after treatment.The observed indicators encompassed coronary angiography findings,the Gensini score for assessing coronary stenosis severity,the inflammatory marker high-sensitivity C-reactive protein(hs-CRP),and lipid profile parameters including total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C).Additionally,the occurrence of adverse reactions during treatment was monitored.Results After treatment,the total effective rate in experimental group was significantly higher than that in control group,with a statistically significant difference(P<0.05).In the comparison of the baseline data,both groups showed marked improvements in CI,CO,LVEF,and HDL-C.However,at the same time points,the experimental group demonstrated significantly better results in these parameters than control group(P<0.05).Additionally,LVEDD,LDL-C,hs-CRP and Gensini scores were significantly reduced after treatment in both groups compared to pretreatment levels.Moreover,at identical time points,the aforementioned parameters in the experimental group demonstrated significantly greater reductions compared to control group(P<0.05).Regarding safety assessment,comparative analysis of adverse drug reaction(ADR)incidence rates between the two treatment groups revealed no statistically significant difference(P>0.05).Conclusions In patients with CHD complicated by hyperlipidemia,ezetimibe demonstrates significant therapeutic advantages.It effectively enhances treatment efficacy,regulates lipid profiles,improves cardiac function,and mitigates the progression of atherosclerosis.This regimen exhibits a favorable safety profile and holds substantial clinical value for both therapeutic processes and rehabilitation outcomes in this patient population.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
Atherosclerosis(AS)is the core pathological basis of Cardiovascular Disease(CVD)worldwide.Its occurrence and development involve endothelial dysfunction,lipid deposition,chronic inflammation and abnormal proliferation...Atherosclerosis(AS)is the core pathological basis of Cardiovascular Disease(CVD)worldwide.Its occurrence and development involve endothelial dysfunction,lipid deposition,chronic inflammation and abnormal proliferation of smooth muscle cells.Berberine(BBR),also known as berberine,is an isoquinoline alkaloid extracted from traditional Chinese medicine such as Coptis coptidis and Phelloberia angustifolia.It has traditionally been used for antibacterial and anti-inflammatory treatment.In recent years,it has been found that it has multi-target metabolic regulation and anti-inflammatory properties,showing significant potential in the prevention and treatment of AS.This article systematically reviews the research progress of berberine in the treatment of AS by improving endothelial function,regulating lipid metabolism,inhibiting inflammatory response,regulating smooth muscle cell phenotypic transformation,and anti-oxidative stress,and discusses the current status and challenges of its clinical application.展开更多
Aim To investigate the anti-atherosclerotic mechanisms of the novel compoundpivanampeta in the early and later stages of atherosclerosis evolution. Methods Rats or rabbits wererandomly assigned to the control, the mod...Aim To investigate the anti-atherosclerotic mechanisms of the novel compoundpivanampeta in the early and later stages of atherosclerosis evolution. Methods Rats or rabbits wererandomly assigned to the control, the model and the pivanampeta-treated groups. The rats or rabbitsin the model group and the pivanampeta-treated group were fed with hypercholesterol diet. Thecarotids of rabbits were cut into pieces and stained with HE. The rat or rabbit serum levels of TC,LDL-CHO, HDL-CHO, IL-8, ET-1, PGI_2, TXA_2, and NO were assayed. The expressions of MCP-1 and IL-8mRNA on rabbit carotid were determined by semi-quantitative RT-PCR. Results Pivanampeta exerted aninhibitory effect on TXA_2 formation without PGI_2 production in the early and later stages ofatherosclerosis. The significantly increased release of NO and the decreased release of IL-8 in theanimals in pivanampeta-treated group were both detected in the rat atherosclerosis model. In therabbit atherosclerosis model the expressions of IL-8 and MCP-1 mRNA in pivanampeta-treated groupwere decreased significantly. However, the treatment with pivanampeta had no effect on the levels ofplasma cholesterol, MDA and SOD. Conclusion The increase of serum NO contents and the decrease ofplasma TXA_2 level, as well as its inhibition of expression of IL-8 and MCP-1 are probably involvedin the mechanisms underlying the anti-atherosclerotic effects of pivanampeta.展开更多
The reasons for the formation of atherosclerosis are diverse and complex,and atherosclerosis as a kind of systemic disease has the characteristics of focal selectivity,which occurs in the carotid bifurcation.The featu...The reasons for the formation of atherosclerosis are diverse and complex,and atherosclerosis as a kind of systemic disease has the characteristics of focal selectivity,which occurs in the carotid bifurcation.The feature enables a large number of studies have found that the severe local hemodynamic characteristics has a great influence to the occurrence of this disease.This paper briefly reviews the related research on the local hemodynamics of carotid bifurcation.The relevant parameters of local hemodynamics were sorted out and summarized,and the effects of wall shear force and its derived parameters on the generation,progression and rupture of carotid atherosclerosis and their clinical applications were reviewed,in order to provide mechanical information for the early warning of carotid plaque rupture.At the same time,this paper describes the transformation of local hemodynamics research in the clinical application of carotid atherosclerosis disease,in order to provide personalized selection and basis for the clinical treatment of this disease.展开更多
Objective: this study aims to explore a new clinical multiparameter diagnostic formula for lower limb atherosclerotic stenosis / occlusion based on the retrospective data of 429 patients at Peking University Hospital....Objective: this study aims to explore a new clinical multiparameter diagnostic formula for lower limb atherosclerotic stenosis / occlusion based on the retrospective data of 429 patients at Peking University Hospital. Methods: this study is a retrospective study. A number of patients with color Doppler ultrasound from November 2013 to October 2021 and improved the test and measurement of common risk factors for atherosclerosis in the same period. A total of 429 cases were selected as the study data. According to the color Doppler ultrasound results, it was divided into the "normal / plaque group" and the "stenosis / occlusion group", including 300 cases in the "normal / plaque group" and 129 cases in the stenosis / occlusion group. Variables included in the diagnostic model screening in this study included age, sex, BMI, ApoA1, ApoB, HbA1c, Hcy, SUA, T C, L DL-C, H DL-C, TG, and blood pressure. Diagnostic models were constructed using logistic regression for variable screening using backward methods. Diagnostic efficacy was evaluated using ROC curves for both single measures and the final diagnostic formula. Results: after a variable screening, The final diagnostic formula is as follows: 0.07 Age (year) + Gender (male value of 0);Female value of-1.38) + HDL-C (normal value of 0;Low side to take a value of 0.79;High value-0.71) + ApoA1 (normal value 0;Low side to take the value of-0.75;High value-0.04) + HbA1c (normal value 0;High value 0.54) + SUA (normal value 0;High value-1.19) + B P (normal value 0;Normal high value value-0.67;Hypertension values were taken at 0.11) -5.17. The optimal threshold of this diagnostic formula is-0.852, specificity of 0.713, sensitivity of 0.760, and the area under the ROC curve is 0.79, which is greater than the area under the R OC curve of any single index in the diagnostic formula. It is a new index of more diagnostic value than other single risk factor indicators in the formula. Conclusion: the diagnosis of lower limb atherosclerotic stenosis / occlusion is of good clinical utility, and the first attempt to use the integration of atherosclerosis risk factors for multiple parameters, and then derive a new diagnostic index, providing a new idea and method for the prevention and treatment of atherosclerosis.展开更多
Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and...Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and study methods along with potential confounders have yielded conflicting results. Infection triggers a chronic inflammatory state which along with other mechanisms such as dyslipidemia, hyper-homocysteinemia, hypercoagulability, impaired glucose metabolism and endothelial dysfunction, contribute in pathogenesis of atherosclerosis. Studies have shown a positive relations between Cytotoxic associated gene-A positive strains of Helicobacter pylori and vascular diseases such as coronary artery disease and stroke. Infection mediated genetic modulation is a new emerging theory in this regard. Further large scale studies on infection and atherosclerosis focusing on multiple pathogenetic mechanisms may help in refining our knowledge in this aspect.展开更多
基金the Ministry of Science and Technology Taiwan,No.MOST 109-2314-B-182A-091,No.NSTC 112-2314-B-182A-062, No.NSTC 113-2314-B-182A-125.
文摘BACKGROUND The incidence of diabetic atherosclerosis(DMA)is increasing worldwide,but its pathogenesis remains incompletely understood.In addition to cardiovascular complications,bladder dysfunction is one of the common comorbidities associated with DMA but is often refractory to current treatments.AIM To investigate the therapeutic effect of human amniotic fluid stem cell-derived extracellular vesicles(hAFSC-EVs)on the recovery of bladder dysfunction in DMA rats.METHODS Eighty rats were divided into normal control,streptozotocin-induced diabetic rats,diabetic rats subjected to arterial balloon endothelial injury of common iliac artery(DMA),and DMA rats treated with hAFSC-EVs(DMA+hAFSC-EVs).At 4 weeks and 12 weeks after DMA induction,levels of blood glucose,total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,homeostasis model assessment(HOMA)-insulin resistance,and HOMA-βwere measured.Cystometry,common iliac artery wall thickness,and bladder tumor necrosis factor(TNF)-α,interleukin(IL)-6,transforming growth factor(TGF)-β1,Smad3,connective tissue growth factor(CTGF)and fibronectin were also evaluated.RESULTS Bladder weight and blood glucose,triglyceride,HOMA-insulin resistance,common iliac artery intima thickness,voided volume,intercontraction interval,bladder capacity,and mRNA expression of TNF-α,IL-6,TGF-β1,Smad3,CTGF and fibronectin were significantly increased at 4 weeks and 12 weeks after induction,while the HOMA-βlevel decreased at 4 weeks and 12 weeks,and the high-density lipoprotein cholesterol level decreased at 12 weeks.hAFSC-EVs treatment in DMA rats significantly reduced bladder weight and blood glucose,thickness of common iliac arterial intima,voided volume,intercontraction interval and bladder capacity at 4 weeks.The mRNA expression of TNF-α,TGF-β1,and CTGF in DMA rats treated with hAFSC-EVs were significantly decreased at 4 weeks,while the mRNA expressions of IL-6 and Smad3 were significantly decreased 12 weeks.CONCLUSION hAFSC-EVs treatment can help restore DMA-induced bladder dysfunction,which is associated with lowered blood glucose levels,reduced arterial wall thickness,and decreased TNF-α,IL-6,TGF-β1,Smad3,and CTGF expression.
文摘Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and treated with OA,and the levels of cell proliferation,migration,adhesion,and apoptosis were evaluated by BrdU staining,scratch healing assay,monocyte-endothelial cell adhesion assay and flow cytometry.The mice were fed with a high-fat diet to induce an atherosclerosis model,and treated with OA by gastric gavage.The mice were divided into the control group,the model group,and the OA administration group.The blood lipid and plaque formation in mice were detected.In addition,oxidative stress and mitochondrial structure and function changes in cells and mice were evaluated by transmission electron microscopy,JC-1 fluorescent probe,and Western blotting assays.The expression levels of proteins in the AMPK/Drp1 pathway were examined through Western blot.Results:OA markedly increased cell viability and migration rate of HUVECs,and decreased the adhesion rate of THP-1 cells and the apoptosis rate.OA significantly reduced serum lipid levels,such as total cholesterol and triglyceride,in mice and inhibited plaque formation in the aorta.OA also significantly increased the content of superoxide dismutase and catalase,alleviated mitochondrial damage,such as mitochondrial swelling and mitochondrial cristae reduction,reduced the number of mitochondria,increased adenosine triphosphate content,and significantly reduced p-Drp1(Ser616)/Drp1,MFF and FIS1 levels,increased p-AMPK/AMPK levels,activated AMPK,and then regulated DRP1 activity.Conclusions:OA activates AMPK,which in turn regulates the activity of DRP1 to restore normal mitochondrial dynamics and reduce atherosclerosis.
基金funded by the Yancheng Municipal Health Commission 2024 Medical Research Project(YK2024166).
文摘Objective:To investigate the anti-atherosclerosis effect of chikusetsusaponinⅣ(CSⅣ)against high-fat diet-induced atherosclerosis in rats.Methods:A high-fat diet was used for the induction of atherosclerosis in rats,and the rats received oral CSⅣor atorvastatin.The body weight,organ weights,food intake,calorie intake,lipid parameters,3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA)/mevalonate ratio,collagen,free fatty acid,cardiac parameters,apolipoprotein(A and B),antioxidant parameters,inflammatory cytokines,and inflammatory parameters were assessed.The mRNA expressions of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),IL-6,IL-17,PI3K,AKT,and mTOR were estimated.Results:CSⅣsignificantly modulated food intake,body weight,organ weight(liver,kidney,and heart),and calories(P<0.05).Total cholesterol,triglycerides,very low-density lipoprotein cholesterol,low-density lipoprotein cholesterol,cardiovascular risk index-1,and cardiovascular risk index-2 were decreased,while high-density lipoprotein cholesterol and anti-atherogenic index were increased significantly in the CSⅣgroup(P<0.05).Besides,CSⅣsignificantly restored the level of HMG-CoA/mevalonate ratio,collagen,free fatty acid,cardiac parameters(creatinine kinase-MB,lactate dehydrogenase,cTnT,cTnI),apolipoprotein(apolipoprotein A and apolipoprotein B),antioxidant parameters(MDA,CAT,GPx,GSH,SOD),inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-10),inflammatory parameters(COX-2,TGF-β,NF-κB),intercellular adhesion molecule-1,vascular cell adhesion molecule-1,and monocyte chemoattractant protein-1.CSⅣalso decreased the mRNA expression of IL-1β,TNF-α,IL-6,IL-17,PI3K,AKT,and mTOR.Conclusions:This study showed the anti-atherosclerosis effect of CSⅣagainst high-fat diet-induced atherosclerosis in rats via alteration of NF-κB/COX-2 and PI3K/AKT/mTOR signaling pathway.
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.
文摘Background In recent years,the incidence of coronary heart disease(CHD)has continued to rise,and its comorbidity with hyperlipidemia significantly increases the mortality risk in patients.Statin monotherapy faces limitations in efficacy for some patients and raises potential safety concerns.Ezetimibe,as a novel lipid-modulating agent,exhibits potential advantages in the treatment of hyperlipidemia.Based on this,the present study investigated the therapeutic efficacy of ezetimibe in CHD patients with hyperlipidemia,as well as its effects on lipid metabolism and the amelioration of atherosclerosis.Methods In this study,150 clinical cases with CHD and hyperlipidemia admitted in our hospital from July 2022 to July 2024 were collected for retrospective analysis.According to different treatment methods,they were randomly divided into the Atorvastatin group(control group,n=75)and the Atorvastatin+Ezetimibe group(experimental group,n=75).Control group received atorvastatin monotherapy,while experimental group were administered additional ezetimibe as an adjunct to the atorvastatin-based treatment regimen.The clinical efficacy of the two treatment groups was analyzed,including cardiac function-related parameters such as the cardiac index(CI),cardiac output(CO),left ventricular ejection fraction(LVEF)and left ventricular end-diastolic diameter(LVEDD)before and after treatment.The observed indicators encompassed coronary angiography findings,the Gensini score for assessing coronary stenosis severity,the inflammatory marker high-sensitivity C-reactive protein(hs-CRP),and lipid profile parameters including total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C).Additionally,the occurrence of adverse reactions during treatment was monitored.Results After treatment,the total effective rate in experimental group was significantly higher than that in control group,with a statistically significant difference(P<0.05).In the comparison of the baseline data,both groups showed marked improvements in CI,CO,LVEF,and HDL-C.However,at the same time points,the experimental group demonstrated significantly better results in these parameters than control group(P<0.05).Additionally,LVEDD,LDL-C,hs-CRP and Gensini scores were significantly reduced after treatment in both groups compared to pretreatment levels.Moreover,at identical time points,the aforementioned parameters in the experimental group demonstrated significantly greater reductions compared to control group(P<0.05).Regarding safety assessment,comparative analysis of adverse drug reaction(ADR)incidence rates between the two treatment groups revealed no statistically significant difference(P>0.05).Conclusions In patients with CHD complicated by hyperlipidemia,ezetimibe demonstrates significant therapeutic advantages.It effectively enhances treatment efficacy,regulates lipid profiles,improves cardiac function,and mitigates the progression of atherosclerosis.This regimen exhibits a favorable safety profile and holds substantial clinical value for both therapeutic processes and rehabilitation outcomes in this patient population.
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.
文摘Atherosclerosis(AS)is the core pathological basis of Cardiovascular Disease(CVD)worldwide.Its occurrence and development involve endothelial dysfunction,lipid deposition,chronic inflammation and abnormal proliferation of smooth muscle cells.Berberine(BBR),also known as berberine,is an isoquinoline alkaloid extracted from traditional Chinese medicine such as Coptis coptidis and Phelloberia angustifolia.It has traditionally been used for antibacterial and anti-inflammatory treatment.In recent years,it has been found that it has multi-target metabolic regulation and anti-inflammatory properties,showing significant potential in the prevention and treatment of AS.This article systematically reviews the research progress of berberine in the treatment of AS by improving endothelial function,regulating lipid metabolism,inhibiting inflammatory response,regulating smooth muscle cell phenotypic transformation,and anti-oxidative stress,and discusses the current status and challenges of its clinical application.
文摘Aim To investigate the anti-atherosclerotic mechanisms of the novel compoundpivanampeta in the early and later stages of atherosclerosis evolution. Methods Rats or rabbits wererandomly assigned to the control, the model and the pivanampeta-treated groups. The rats or rabbitsin the model group and the pivanampeta-treated group were fed with hypercholesterol diet. Thecarotids of rabbits were cut into pieces and stained with HE. The rat or rabbit serum levels of TC,LDL-CHO, HDL-CHO, IL-8, ET-1, PGI_2, TXA_2, and NO were assayed. The expressions of MCP-1 and IL-8mRNA on rabbit carotid were determined by semi-quantitative RT-PCR. Results Pivanampeta exerted aninhibitory effect on TXA_2 formation without PGI_2 production in the early and later stages ofatherosclerosis. The significantly increased release of NO and the decreased release of IL-8 in theanimals in pivanampeta-treated group were both detected in the rat atherosclerosis model. In therabbit atherosclerosis model the expressions of IL-8 and MCP-1 mRNA in pivanampeta-treated groupwere decreased significantly. However, the treatment with pivanampeta had no effect on the levels ofplasma cholesterol, MDA and SOD. Conclusion The increase of serum NO contents and the decrease ofplasma TXA_2 level, as well as its inhibition of expression of IL-8 and MCP-1 are probably involvedin the mechanisms underlying the anti-atherosclerotic effects of pivanampeta.
基金Health Industry Scientific Research Project of Hainan Province(20A200219)。
文摘The reasons for the formation of atherosclerosis are diverse and complex,and atherosclerosis as a kind of systemic disease has the characteristics of focal selectivity,which occurs in the carotid bifurcation.The feature enables a large number of studies have found that the severe local hemodynamic characteristics has a great influence to the occurrence of this disease.This paper briefly reviews the related research on the local hemodynamics of carotid bifurcation.The relevant parameters of local hemodynamics were sorted out and summarized,and the effects of wall shear force and its derived parameters on the generation,progression and rupture of carotid atherosclerosis and their clinical applications were reviewed,in order to provide mechanical information for the early warning of carotid plaque rupture.At the same time,this paper describes the transformation of local hemodynamics research in the clinical application of carotid atherosclerosis disease,in order to provide personalized selection and basis for the clinical treatment of this disease.
文摘Objective: this study aims to explore a new clinical multiparameter diagnostic formula for lower limb atherosclerotic stenosis / occlusion based on the retrospective data of 429 patients at Peking University Hospital. Methods: this study is a retrospective study. A number of patients with color Doppler ultrasound from November 2013 to October 2021 and improved the test and measurement of common risk factors for atherosclerosis in the same period. A total of 429 cases were selected as the study data. According to the color Doppler ultrasound results, it was divided into the "normal / plaque group" and the "stenosis / occlusion group", including 300 cases in the "normal / plaque group" and 129 cases in the stenosis / occlusion group. Variables included in the diagnostic model screening in this study included age, sex, BMI, ApoA1, ApoB, HbA1c, Hcy, SUA, T C, L DL-C, H DL-C, TG, and blood pressure. Diagnostic models were constructed using logistic regression for variable screening using backward methods. Diagnostic efficacy was evaluated using ROC curves for both single measures and the final diagnostic formula. Results: after a variable screening, The final diagnostic formula is as follows: 0.07 Age (year) + Gender (male value of 0);Female value of-1.38) + HDL-C (normal value of 0;Low side to take a value of 0.79;High value-0.71) + ApoA1 (normal value 0;Low side to take the value of-0.75;High value-0.04) + HbA1c (normal value 0;High value 0.54) + SUA (normal value 0;High value-1.19) + B P (normal value 0;Normal high value value-0.67;Hypertension values were taken at 0.11) -5.17. The optimal threshold of this diagnostic formula is-0.852, specificity of 0.713, sensitivity of 0.760, and the area under the ROC curve is 0.79, which is greater than the area under the R OC curve of any single index in the diagnostic formula. It is a new index of more diagnostic value than other single risk factor indicators in the formula. Conclusion: the diagnosis of lower limb atherosclerotic stenosis / occlusion is of good clinical utility, and the first attempt to use the integration of atherosclerosis risk factors for multiple parameters, and then derive a new diagnostic index, providing a new idea and method for the prevention and treatment of atherosclerosis.
文摘Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and study methods along with potential confounders have yielded conflicting results. Infection triggers a chronic inflammatory state which along with other mechanisms such as dyslipidemia, hyper-homocysteinemia, hypercoagulability, impaired glucose metabolism and endothelial dysfunction, contribute in pathogenesis of atherosclerosis. Studies have shown a positive relations between Cytotoxic associated gene-A positive strains of Helicobacter pylori and vascular diseases such as coronary artery disease and stroke. Infection mediated genetic modulation is a new emerging theory in this regard. Further large scale studies on infection and atherosclerosis focusing on multiple pathogenetic mechanisms may help in refining our knowledge in this aspect.
