Atherosclerosis(As)poses a serious threat to human health,and modern medicine still faces many limi-tations in its treatment of this disease.However,components and compounds of traditional Chinese medicine(TCM)have unique advantages in anti-atherosclerosis by regulating macrophage autophagy,they exert anti-inflammatory,anti-oxi-dation,lipid metabolism-regulating and plaque-stabilizing effects.This paper reviews the application of TCM in regulating macrophage autophagy to prevent and treat atherosclerosis,and provides new insights into the application of TCM compo-nents and compounds in the treatment of As.

Aim To evaluate the tyrosine nitration modification of specific proteins in vascular endothelial cells and its impact on mitochondria-mediated apoptosis.Methods Human umbilical vein endothelial cells were cultured in vitro and divided into three groups:control group(treatment with dimethyl sulfoxide),3-morphansulam(SIN-1)group,and SIN-1+Fe(Ⅲ)5,10,15,20-(tetraphenyl)porphyrin(FeTPP)group.After 24 h,the levels of hexokinase 1(HK1)nitration modification,mitochondrial membrane potential,reactive oxygen species(ROS)production,and endothelial cell proliferation and apoptosis were assessed.A human umbilical vein endothelial cell line knockout of HK1 was constructed using gene editing technology,and its proliferation and apoptosis levels were detected.Results After treatment of hu-man umbilical vein endothelial cells with peroxynitrite generator SIN-1,the level of HK1 protein nitration modification sig-nificantly increased(P＜0.01),reactive oxygen species production significantly increased,mitochondrial membrane poten-tial significantly decreased,endothelial cell proliferation ability significantly decreased,and endothelial cell apoptosis level significantly increased(all P＜0.01).Peroxynitrite decomposition catalyst FeTPP could reverse the above effect(P＜0.01).In addition,HK1 gene knockout also exhibited similar antioxidant effects,with a significant decrease in endothe-lial cell proliferation ability and a significant increase in apoptosis levels(P＜0.01).Conclusion Peroxynitrite can induce an increase in the level of nitration modification of HK1 in vascular endothelial cells,which may be achieved by pro-moting the production of mitochondrial reactive oxygen species,thereby accelerating the process of endothelial cell apoptosis.

Aim Systematic evolution of ligands by exponential enrichment(SELEX)techniquewas employed to screen and identify nucleic acid aptamers that specifically bind to mouse atherosclerotic pathological tissues,aiming to pro-vide a research foundation for the development of molecular targets and diagnostic reagents for early atherosclerosis.Methods A single-stranded DNA(ssDNA)library with a capacity of 1015～1016 was constructed,which was then subjec-ted to binding-elution(negative selection)with normal mouse vascular tissue slices.The eluted library was subsequently bound to atherosclerotic tissue slices for binding-elution(positive selection).PCR was used to amplify the positive and negative screening products,and agarose gel electrophoresis was used to verify the amplified products.The ssDNA library after multiple rounds of selection was sequenced using T-A cloning and sequencing to obtain the primary structure of the nu-cleic acid aptamers,and the secondary structure was predicted using the Mfold online software.The selected nucleic acid aptamers were labeled with a FAM fluorescent group at the 5'-end and were bound to both positive and negative selection tissue slices,with fluorescence intensity observed under a fluorescence microscope.Image Pro Plus 6.0 was used to cal-culate the relative average fluorescence intensity to evaluate the binding specificity of nucleic acid aptamers.Results After 8 rounds of selection,agarose gel electrophoresis imaging showed PCR amplification products in the positive selection lanes,while no PCR amplification products were observed in the negative selection lanes,indicating the successful acquisi-tion of a nucleic acid aptamer library that specifically binds to atherosclerotic tissues.Five nucleic acid aptamers were i-dentified by T-A cloning and sequencing,and their predicted secondary structures all had stem-loop structures.Immuno-fluorescence staining verified that five nucleic acid aptamers had different degrees of binding with As blood vessels,and the quantitative results of the relative average fluorescence intensity showed that nucleic acid aptamer No.11 had the highest relative average fluorescence intensity value,which can be used as a candidate nucleic acid aptamer for subsequent re-search.Conclusion Specific nucleic acid aptamers that bind to atherosclerotic vesselswere successfully obtained,providing a research foundation for further screening of early molecular targets of Asand developing in vivo early diagnostic reagents.

Aim To explore the risk factors for the progressive worsening of moderate coronary stenosis and con-struct a nomogram model for predicting the progression of moderate coronary stenosis based on coronary CT-fractional flow reserve(FFR).Methods 293 patients with moderate coronary stenosis admitted to the hospital from April 2020 to A-pril 2023 were selected as the research subjects.Coronary CT angiography(CCTA)was performed on the selected pa-tients,and CT-FFR software was used to analyze the CCTA images and obtain the FFR values.According to the progres-sive worsening of moderate coronary stenosis,the patients were divided into two groups:the progression group and the sta-ble group,and the data of gender,age,hyperlipidemia,history of cerebral infarction,multivessel disease,obesity,diabe-tes,malnutrition,lack of physical activity,hypertension,drinking,smoking and place of residence of the patients in the two groups were collected.The ten-fold cross-validation in LASSO analysis was used to screen for predictive factors of progressive worsening of moderate coronary stenosis,Logistic regression was used to screen for risk factors of progressive worsening of moderate coronary stenosis,R(4.2.3)was used to establish a nomogram model of progressive worsening of moderate coronary stenosis,and this nomogram model was validated.Results Among 293 patients with moderate cor-onary stenosis,there were 61 cases of progressive worsening,and the incidence of progressive worsening of moderate coro-nary stenosis was 20.82％(61/293).The sex,age,hyperlipidemia,history of cerebral infarction,multi vessel disease,malnutrition,hypertension,alcohol consumption and place of residence of the progression group and the stable group had no statistical significance(P＞0.05),while the proportion of obesity,diabetes,lack of physical activity and smoking in the progression group was significantly higher than those in the stable group,and the FFR was significantly lower than that in the stable group(P＜0.05).LASSO analysis showed that the history of cerebral infarction,obesity,diabetes,lack of physical activity,smoking and FFR were predictive factors with non-zero coefficients.After ten-fold cross-validation,six variables including the history of cerebral infarction,obesity,diabetes,lack of physical activity,smoking and FFR were re-tained into the model.Logistic regression analysis showed that obesity(OR=2.411,95％CI:1.151～5.053),diabetes(OR=3.401,95％CI:1.671～6.923),lack of physical activity(OR=2.818,95％CI:1.427～5.564),smoking(OR=3.577,95％CI:1.526～8.387)were all risk factors for progressive worsening of moderate coronary stenosis,and FFR(OR=0.001,95％CI:0.000～0.036)was the antagonistic factor for progressive worsening of moderate coronary stenosis(P＜0.05).A dynamic nomogram model for the progressive worsening of moderate coronary stenosis was established based on risk factors,and the area under the ROC curve of the nomogram model was 0.777(95％CI:0.711～0.842);The predicted values of the calibration curve are basically consistent with the actual values;When the decision curve showed a threshold probability of 2％to 64％,the nomogram model had a good benefit value for predicting the progressive worsening of moderate coronary stenosis.Conclusion The nomogram model constructed in this study has high accuracy in predicting the progression of moderate coronary stenosis and good clinical practicality.

Aim To investigate the association of triglyceride-glucose(TyG)index with microvascular obstruction(MVO)after percutaneous coronary intervention(PCI)in patients with ST-segment elevated myocardial infarction(STEMI).Methods Individual patient-data were pooled from 310 patients with STEMI underwent emergency PCI in Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School from June 2018 to June 2021 for a prospective analysis.A week following the operation,cardiac magnetic resonance imaging was used to evaluate the MVO region and the patients were divided into two groups based on whether MVO occured after PCI:the MVO group(n=183)and the non-MVO group(n=127).The clinical data of the two groups were compared,and the linear relationship between TyG index and MVO was described using restricted cubic splines(RCS).Univariate and multivariate Logistic regression analysis were used to correct for confounding factors and identify independent risk factors for MVO occurrence.Results After adjustment for confounding factors,TyG index was an independent risk factor for MVO after emergency PCI in STEMI patients,and every 1-unit increased in TyG index,the risk of MVO increased by 1.24 times(OR=2.24,95％CI:1.07～4.71,P=0.033).The RCS curve analysis results showed that there was a linear re-lationship between the TyG index and the occurrence of MVO after emergency PCI(non-linear correlation test P=0.47).When the TyG index was greater than 9.5,the risk of MVO after emergency PCI significantly increased.Conclusion An increased TyG index is postively associated with the incidence of MVO in STEMI patients who have undergone PCI,and has clinical significantce for early prevention and risk stratification of MVO in STEMI patients.

Proprotein convertase subtilisin/kexin type 9(PCSK9)can modulate low density lipoprotein cholesterol(LDLC)levels,and its dysfunction is closely associated with the progression of atherosclerosis and cardiovascular diseases.Research has shown that PCSK9 inhibitors are highly effective in lowering lipids and have good safety and tolerability.New approaches to targeting PCSK9 inhibition are currently in different stages of clinical development.This review out-lines the primary mechanisms of PCSK9 and its impact on the cardiovascular system,emphasizing the current emerging strategies for targeting PCSK9 in lipid-lowering treatments.

Atherosclerosis is recognized as an inflammatory disease,and its development is regulated by multiple fac-tors,particularly dyslipidemia.Peroxisome proliferator-activated receptor(PPAR)regulate the expression of genes that are involved in lipid metabolism and inflammation;and they have three subfamily members including PPARα,PPARβ,and PPARγ.However,synthetic PPAR agonists exhibit ambiguous effects in atherosclerotic therapy and induce various side effects.Notably,recent studies demonstrate that traditional Chinese medicine(TCM)alleviate atherosclerotic cardiovascular diseases via suppressing hyperlipidemia and inflammation through regulation of PPAR signaling pathway.This article pri-marily reviews the regulatory effects of TCM on PPAR and their therapeutic effects on atherosclerosis,provides valuable in-formation for pharmacologists that are interested in searching for effective herbal prescriptions for atherosclerosis therapy and for clinicians that are interested in prevention and treatment of atherosclerotic cardiovascular diseases using TCM.

Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.

Cardiovascular diseases have become the leading cause of mortality worldwide.The gut microbiota and its metabolites play an important role in the occurrence and development of cardiovascular diseases,and an imbalance of gut microbiota and its metabolites can promote the progression of cardiovascular diseases.Phenylacetylglutamine is a phenyl-alanine metabolite of intestinal flora.More and more studies have shown that phenylacetylglutamine is an independent risk factor of cardiovascular diseases and a potential biomarker of cardiovascular diseases.It is involved in the pathogenesis of cardiovascular diseases,such as arrhythmia,heart failure,atherosclerosis,etc.Therefore,interventions targeting pheny-lacetylglutamine are expected to become a new strategy for treating cardiovascular diseases.This review focuses on the role of phenylacetylglutamine in the occurrence and development of several common cardiovascular diseases.

Angiogenesis within atherosclerotic plaques is a critical determinant of plaque stability.The biome-chanical microenvironment,consisting of fluid shear force,plaque structural stress,and matrix stiffness,serves as signifi-cant factors in mediating plaque angiogenesis.Endothelial cells respond to mechanical signals and participate in plaques neovascularization through force chemical signal transduction mechanisms.This review provides an overview of the mecha-nisms by which mechanical factors regulate angiogenesis within plaques and offers a novel therapeutic approach for the pre-vention and treatment of atherosclerosis.