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
Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary in...Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.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
Objective:To explore the value of TCD and CDUS on diagnosis of large artery atherosclerosis.Methods:In our study,90 patients who had been admitted to our hospital and diagnosed as LAA according to CISS typing were sel...Objective:To explore the value of TCD and CDUS on diagnosis of large artery atherosclerosis.Methods:In our study,90 patients who had been admitted to our hospital and diagnosed as LAA according to CISS typing were selected as the research object.A retrospective analysis was conducted,using CTA as golden standard for diagnoses of stenoses.Explore the risk factors of LAA,the reliability of TCD and CDUS in diagnosis of the stenosis and distribution of stenosis in each vessel.Results:Hypertension and type 2 diabetes are risk factors of LAA vascular stenosis.Middle cerebral artery stenosis detection by TCD carries the highest reliability(sensitivity 90.91%,specificity 97.89%,positive predictive value 96.15%,the negative predictive value was 94.9%,the positive likelihood ratio was 43.18,negative likelihood ratio 0.09,Kappa=0.9).The consistency of TCD is as good as CTA in head and neck part.The negative coincidence rate was higher in the anterior circulation vessels(97.98%),followed by the coincidence rate of severe stenosis(95.23%).However,the detection rate of posterior circulation vessels positive,moderate and severe stenosis,mild stenosis gradually decreased by TCD.CDUS carries general reliability in detecting intracranial extracranial stenosis,the highest reliability in internal carotid artery(kappa 0.82),and the worst consistency in vertebral artery(kappa 0.38).The negative coincidence rate of CDUS in extracranial cerebrovascular stenosis was highest(97.22),followed by the overall compliance rate(91.55%).242 branches of vascular stenosis were discovered in our study,among which intracranial artery stenosis 61.15%(148/242)is higher than that in extracranial artery 38.85%(90/242),ratio of moderate to severe stenosis is as high as 82.23%(199/242).Intracranial artery stenosis in ICA is extremely common(51.11%,46/90),and MCA is the common area of intracranial artery stenosis(37.16%,55/148).Conclusions:(1)Hypertension,type 2 diabetes are risk factors for LAA stenosis.(2)TCD detection of intracranial vascular stenosis carries the best consistency,and reliability of MCA is the highest.In our search,MCA possesses the highest rate of stenosis,and negative coincidence rate by TCD examination was the highest,which could be used for screening method for stenosis.The reliability of TCD in diagnosis of moderate and severe stenosis was relatively better than mild stenosis.(3)CDUS detection of anterior circulation lesions is better than that of posterior circulation lesions.Evaluate effect on moderate and severe stenosis was better than that of mild one.The ratio of ICA stenosis was the highest,but the effect on VA was poor.(4)The incidence of intracranial vascular stenosis is more common than that of the intracranial vascular stenosis.展开更多
Atherosclerosis(AS), mainly caused by the changed immune system functions and inflammation, is the central pathogenesis of cardiovascular disease, which is a leading cause of death in the world. In modern medicine, th...Atherosclerosis(AS), mainly caused by the changed immune system functions and inflammation, is the central pathogenesis of cardiovascular disease, which is a leading cause of death in the world. In modern medicine, the development of carriers precisely delivering the therapeutic agents to the target sites is the primary goal, which could minimize the potential adverse effects and be more effective in treating lesions. Due to the precise location, real-time monitoring, AS microenvironment response, and low toxicity, stimuli-responsive nano-based drug delivery systems(NDDSs) have been a promising approach in AS treatments. Herein, we will systematically summarize the recent advances in stimuli-responsive NDDSs for AS treatment, including internal stimuli(reactive oxygen species, enzyme, shear stress, and pH) and external stimuli(light, ultrasound, and magnetism) responsive NDDSs. Besides, we will also summarize in detail the classification of stimuli-responsive NDDSs for AS, such as organic NDDSs(e.g., lipid-based and polymer-based nanomaterials), inorganic NDDSs(e.g., metal-based nanoparticles and nonmetallic nanomaterials), and composite multifunctional NDDSs. Finally, the critical challenges and prospects of this field will also be proposed and discussed.展开更多
Intracranial atherosclerotic disease (ICAD) represents a major cause of stroke and transient ischemic attacks. The prevalence and natural course of ICAD are closely related to race and ethnicity. The best treatment fo...Intracranial atherosclerotic disease (ICAD) represents a major cause of stroke and transient ischemic attacks. The prevalence and natural course of ICAD are closely related to race and ethnicity. The best treatment for ICAD is a crucial issue;data from recent trials indicate that aggressive medical management and life style modifications are better than endovascular treatments for prevention of recurrent stroke in high-risk patients with ICAD. Endovascular treatment is still an option for subgroup of patients who are not responded to optimal medical therapy.展开更多
Objective: To determine the prevalence and risk factors of carotid atherosclerosis among ischemic stroke patients in a tertiary hospital in Burkina Faso. Methodology: This was a descriptive and analytical retrospectiv...Objective: To determine the prevalence and risk factors of carotid atherosclerosis among ischemic stroke patients in a tertiary hospital in Burkina Faso. Methodology: This was a descriptive and analytical retrospective study of patients admitted at neurology department of Yalgado Ouedraogo University Teaching Hospital with ischemic stroke and cerebral large vessel atherosclerosis in the period from January 1, 2012 to December 31, 2016. Results: The prevalence of extracranial carotid atherosclerosis was 23.9%. The mean age of patients was 63.5 years (Range 31 - 90 years). The study population included 65% of men and 35% of women. Hypertension was the most common vascular risk factor (75.6%). Stroke was mostly located in the anterior circulation in 23.9%. Low HDL-C was present in 52% of patients. The majority of plaque was homogeneous (85.2%). Plaque were located in carotid bulbar artery (38.5%) followed by common carotid artery (28.2%) and extracranial internal carotid artery (18.6%). According to cerebral lesion, plaque was bilateral in 45.5%, ipsilateral in 42.3% and contralateral in 12.1% of cases. Tight stenosis was found in 30.1% of patients. There was a significant link between male gender and tight stenosis (p = 0.004). Aspirin was the most antiplatelet therapy used (95.5%). Statin therapy was used in 91% of patients. The mean duration of hospitalization was 12.5 days with a mortality rate of 7.1%. Conclusions: Our study showed that extra carotid atherosclerosis was the most common cause of ischemic stroke in Burkina Faso. Man gender was most represented than women.展开更多
Atherosclerosis,which is defined by plaque accumulation within artery walls,is one of the leading causes of cardiovascular disease and mortality.Although they help control symptoms and slow the condition’s progressio...Atherosclerosis,which is defined by plaque accumulation within artery walls,is one of the leading causes of cardiovascular disease and mortality.Although they help control symptoms and slow the condition’s progression,traditional treatments,including medication,surgery,and lifestyle changes,do not ad dress the underlying pathophysiology.Recent innovations in targeted cell therapy,such as gene editing,stem cell therapy,and exosome-based therapies,present encouraging methods for repairing endothelium damage,lowering in-flammation,and restoring vascular health.This study examines how different therapy approaches are related,highlighting the potential of regenerative medicine to stop the progression of atherosclerosis.Despite the potential of these developments,issues such as financial constraints,regulatory obstacles,patient-specific efficacy variability,and safety concerns must be resolved.More research and technical developments are essential to incorporate these treatments into clinical practice,improve patient outcomes,and reduce the prevalence of cardiovascular disease worldwide.展开更多
Metal-organic frameworks(MOFs)hold promise as theranostic carriers for atherosclerosis.However,to further advance their therapeutic effects with higher complexity and functionality,integrating multiple components with...Metal-organic frameworks(MOFs)hold promise as theranostic carriers for atherosclerosis.However,to further advance their therapeutic effects with higher complexity and functionality,integrating multiple components with complex synthesis procedures are usually involved.Here,we reported a facile and general strategy to prepare multifunctional anti-atherosclerosis theranostic platform in a single-step manner.A custom-designed multifunctional polymer,poly(butyl methacrylate-co-methacrylic acid)branched phosphorylatedβ-glucan(PBMMA-PG),can effectively entrap different MOFs via coordination,simultaneously endow the MOF with enhanced stability,lesional macrophages selectivity and enhanced endosome escape.Sequential ex situ char-acterization and computational studies elaborated the potential mechanism.This facile post-synthetic modifi-cation granted the administered nanoparticles atherosclerotic tropism by targeting Dectin-1+macrophages,enhancing in situ MR signal intensity by 72%.Delivery of siNLRP3 effectively mitigated NLRP3 inflammasomes activation,resulting a 43%reduction of plaque area.Overall,the current study highlights a simple and general approach for fabricating a MOF-based theranostic platform towards atherosclerosis conditioning,which may also expand to other indications targeting the lesional macrophages.展开更多
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.
文摘Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.
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.
文摘Objective:To explore the value of TCD and CDUS on diagnosis of large artery atherosclerosis.Methods:In our study,90 patients who had been admitted to our hospital and diagnosed as LAA according to CISS typing were selected as the research object.A retrospective analysis was conducted,using CTA as golden standard for diagnoses of stenoses.Explore the risk factors of LAA,the reliability of TCD and CDUS in diagnosis of the stenosis and distribution of stenosis in each vessel.Results:Hypertension and type 2 diabetes are risk factors of LAA vascular stenosis.Middle cerebral artery stenosis detection by TCD carries the highest reliability(sensitivity 90.91%,specificity 97.89%,positive predictive value 96.15%,the negative predictive value was 94.9%,the positive likelihood ratio was 43.18,negative likelihood ratio 0.09,Kappa=0.9).The consistency of TCD is as good as CTA in head and neck part.The negative coincidence rate was higher in the anterior circulation vessels(97.98%),followed by the coincidence rate of severe stenosis(95.23%).However,the detection rate of posterior circulation vessels positive,moderate and severe stenosis,mild stenosis gradually decreased by TCD.CDUS carries general reliability in detecting intracranial extracranial stenosis,the highest reliability in internal carotid artery(kappa 0.82),and the worst consistency in vertebral artery(kappa 0.38).The negative coincidence rate of CDUS in extracranial cerebrovascular stenosis was highest(97.22),followed by the overall compliance rate(91.55%).242 branches of vascular stenosis were discovered in our study,among which intracranial artery stenosis 61.15%(148/242)is higher than that in extracranial artery 38.85%(90/242),ratio of moderate to severe stenosis is as high as 82.23%(199/242).Intracranial artery stenosis in ICA is extremely common(51.11%,46/90),and MCA is the common area of intracranial artery stenosis(37.16%,55/148).Conclusions:(1)Hypertension,type 2 diabetes are risk factors for LAA stenosis.(2)TCD detection of intracranial vascular stenosis carries the best consistency,and reliability of MCA is the highest.In our search,MCA possesses the highest rate of stenosis,and negative coincidence rate by TCD examination was the highest,which could be used for screening method for stenosis.The reliability of TCD in diagnosis of moderate and severe stenosis was relatively better than mild stenosis.(3)CDUS detection of anterior circulation lesions is better than that of posterior circulation lesions.Evaluate effect on moderate and severe stenosis was better than that of mild one.The ratio of ICA stenosis was the highest,but the effect on VA was poor.(4)The incidence of intracranial vascular stenosis is more common than that of the intracranial vascular stenosis.
基金financial support from the Young Elite Scientists Sponsorship Program by Tianjin (No. 0701320001)Major Special Project of Tianjin (No. 0402080005)+1 种基金Program for Excellent Innovative Talents in Universities of Hebei Province (No. BJ2021019)Vietnam National University,Ho Chi Minh City (VNU-HCM,NCM2020-28-01)。
文摘Atherosclerosis(AS), mainly caused by the changed immune system functions and inflammation, is the central pathogenesis of cardiovascular disease, which is a leading cause of death in the world. In modern medicine, the development of carriers precisely delivering the therapeutic agents to the target sites is the primary goal, which could minimize the potential adverse effects and be more effective in treating lesions. Due to the precise location, real-time monitoring, AS microenvironment response, and low toxicity, stimuli-responsive nano-based drug delivery systems(NDDSs) have been a promising approach in AS treatments. Herein, we will systematically summarize the recent advances in stimuli-responsive NDDSs for AS treatment, including internal stimuli(reactive oxygen species, enzyme, shear stress, and pH) and external stimuli(light, ultrasound, and magnetism) responsive NDDSs. Besides, we will also summarize in detail the classification of stimuli-responsive NDDSs for AS, such as organic NDDSs(e.g., lipid-based and polymer-based nanomaterials), inorganic NDDSs(e.g., metal-based nanoparticles and nonmetallic nanomaterials), and composite multifunctional NDDSs. Finally, the critical challenges and prospects of this field will also be proposed and discussed.
文摘Intracranial atherosclerotic disease (ICAD) represents a major cause of stroke and transient ischemic attacks. The prevalence and natural course of ICAD are closely related to race and ethnicity. The best treatment for ICAD is a crucial issue;data from recent trials indicate that aggressive medical management and life style modifications are better than endovascular treatments for prevention of recurrent stroke in high-risk patients with ICAD. Endovascular treatment is still an option for subgroup of patients who are not responded to optimal medical therapy.
文摘Objective: To determine the prevalence and risk factors of carotid atherosclerosis among ischemic stroke patients in a tertiary hospital in Burkina Faso. Methodology: This was a descriptive and analytical retrospective study of patients admitted at neurology department of Yalgado Ouedraogo University Teaching Hospital with ischemic stroke and cerebral large vessel atherosclerosis in the period from January 1, 2012 to December 31, 2016. Results: The prevalence of extracranial carotid atherosclerosis was 23.9%. The mean age of patients was 63.5 years (Range 31 - 90 years). The study population included 65% of men and 35% of women. Hypertension was the most common vascular risk factor (75.6%). Stroke was mostly located in the anterior circulation in 23.9%. Low HDL-C was present in 52% of patients. The majority of plaque was homogeneous (85.2%). Plaque were located in carotid bulbar artery (38.5%) followed by common carotid artery (28.2%) and extracranial internal carotid artery (18.6%). According to cerebral lesion, plaque was bilateral in 45.5%, ipsilateral in 42.3% and contralateral in 12.1% of cases. Tight stenosis was found in 30.1% of patients. There was a significant link between male gender and tight stenosis (p = 0.004). Aspirin was the most antiplatelet therapy used (95.5%). Statin therapy was used in 91% of patients. The mean duration of hospitalization was 12.5 days with a mortality rate of 7.1%. Conclusions: Our study showed that extra carotid atherosclerosis was the most common cause of ischemic stroke in Burkina Faso. Man gender was most represented than women.
文摘Atherosclerosis,which is defined by plaque accumulation within artery walls,is one of the leading causes of cardiovascular disease and mortality.Although they help control symptoms and slow the condition’s progression,traditional treatments,including medication,surgery,and lifestyle changes,do not ad dress the underlying pathophysiology.Recent innovations in targeted cell therapy,such as gene editing,stem cell therapy,and exosome-based therapies,present encouraging methods for repairing endothelium damage,lowering in-flammation,and restoring vascular health.This study examines how different therapy approaches are related,highlighting the potential of regenerative medicine to stop the progression of atherosclerosis.Despite the potential of these developments,issues such as financial constraints,regulatory obstacles,patient-specific efficacy variability,and safety concerns must be resolved.More research and technical developments are essential to incorporate these treatments into clinical practice,improve patient outcomes,and reduce the prevalence of cardiovascular disease worldwide.
基金financial support from Seed Funding from Second Affiliated Hospital of Zhejiang University School of Medicine.Z.Liu acknowledges financial support from Academy of Finland(No.340129)Finnish Foundation for Cardiovascular Research.Prof.H.A.Santos acknowledges financial support from Academy of Finland(No.331151)+3 种基金the UMCG Research Funds.H.Gao acknowledges financial support from the Chinese Scholarship Council(No.202006090004)financial support European Union’s Horizon Europe 2021 Research and Innovation Programme for her Marie Skło-dowska-Curie(No.101059391)financial support from National Natural Science Foundation of China(No.52072392,52472290)the financial support from Shanghai Super Post-Doctor Incentive Program(No.2022665).
文摘Metal-organic frameworks(MOFs)hold promise as theranostic carriers for atherosclerosis.However,to further advance their therapeutic effects with higher complexity and functionality,integrating multiple components with complex synthesis procedures are usually involved.Here,we reported a facile and general strategy to prepare multifunctional anti-atherosclerosis theranostic platform in a single-step manner.A custom-designed multifunctional polymer,poly(butyl methacrylate-co-methacrylic acid)branched phosphorylatedβ-glucan(PBMMA-PG),can effectively entrap different MOFs via coordination,simultaneously endow the MOF with enhanced stability,lesional macrophages selectivity and enhanced endosome escape.Sequential ex situ char-acterization and computational studies elaborated the potential mechanism.This facile post-synthetic modifi-cation granted the administered nanoparticles atherosclerotic tropism by targeting Dectin-1+macrophages,enhancing in situ MR signal intensity by 72%.Delivery of siNLRP3 effectively mitigated NLRP3 inflammasomes activation,resulting a 43%reduction of plaque area.Overall,the current study highlights a simple and general approach for fabricating a MOF-based theranostic platform towards atherosclerosis conditioning,which may also expand to other indications targeting the lesional macrophages.
