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The latest advances in targeting PCSK9 therapy in the cardiovascular field

Lin WANG ; Xuan YANG ; Jinze FAN ; Jin'e WU ; Liuyi HAO

Chinese Journal of Arteriosclerosis.2025;33(10):892-900. doi:10.20039/j.cnki.1007-3949.2025.10.009

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.

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Research advances on the correlation between stress hyperglycemia ratio and ischemic heart disease

Jiajia LIN ; Chen QU ; Zhengxia LIU ; Yibing LU

Chinese Journal of Arteriosclerosis.2025;33(9):810-814. doi:10.20039/j.cnki.1007-3949.2025.09.010

Ischemic heart disease(IHD)is a clinical disease characterized by reduced cardiac blood flow and im-balanced myocardial oxygen supply-demand.Previous studies have shown that stress hyperglycemia is associated with in-creased mortality in patients with acute myocardial infarction and heart failure,and is a poor prognostic risk factor for ische-mic heart disease.Stress hyperglycemia ratio(SHR)is a value calculated based on the random blood glucose and glycat-ed hemoglobin levels at admission through a mathematical model.As a novel indicator,it enables more accurate assess-ment of stress hyperglycemia.Recent studies has found that SHR is closely related to coronary artery disease,acute myo-cardial infarction,and heart failure caused by IHD.This article reviews the research progress on the association between SHR and IHD from three aspects.SHR may serve as a biochemical marker for risk stratification,prognosis assessment of IHD.

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A novel screening approach for identifying key genes involved in the regulation of brown adipose tissue thermogenesis

Shengwen WANG ; Wenbin TANG ; Junxiao SHI ; Weiping ZHANG ; Chunchun WEI

Chinese Journal of Arteriosclerosis.2025;33(9):745-753. doi:10.20039/j.cnki.1007-3949.2025.09.002

Aim To systematically elucidate the molecular regulatory network of thermogenic function in brown adipose tissue(BAT)through multi-omics integrative analysis,to discover novel thermogenic regulatory genes and provide novel therapeutic targets for metabolic disorders.Methods A novel methodology for screening key genes regulating thermogenesis in BAT was constructed:First,differential expression analysis was performed on bulk RNA-seq data from murine BAT.Genes meeting the thresholds of ABS(log2FoldChange)＞1 and Padj＜0.05 were identified as differentially expressed genes.Intersectional analysis was then applied to obtain consensus upregulated and downregulated gene sets.Subsequently,scRNA-seq data of brown adipocytes were partitioned into high-expression group and low-expression group based on the expression levels of candidate genes.Differential analysis and gene set enrichment analysis(GSEA)were conducted between these groups to assess the correlation between candidate genes and thermogenic function.Finally,ex-perimental validation of selected candidate genes was performed using quantitative real-time PCR and Western blot.Results Bioinformatics analysis identified 65 thermogenesis-positive correlated genes and 7 thermogenesis-negative corre-lated genes.Subsequent quantitative PCR validation demonstrated that candidate genes Mfsd2a,Me1,Slc25a34,Pfkp,Ankrd9,Hsd17b12,Aldoa,Ctsz and Pcyt2 exhibited upregulation exceeding 5-fold,while Pid1 and Angpt1 showed down-regulation over 50％.All observed expression changes demonstrated statistical significance(P＜0.01)through rigorous hypothesis testing.These findings highlight the potential involvement of these genes in thermogenic regulation,warranting further functional investigations to elucidate their molecular mechanisms in energy metabolism pathways.Conclusions This study established a novel"computational screening → in silico knockout → experimental validation"paradigm for tar-get discovery,systematically unveiling the molecular network involved in BAT thermogenic regulation.This methodology is equally applicable for identifying key regulatory genes in other physiological or pathological processes.The study identi-fied 11 core genes that may play pivotal regulatory roles during BAT thermogenic activation,which could potentially offer novel pharmacological intervention targets to improve energy metabolism and treat obesity-related complications.

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Research status of cardiovascular disease risk in metabolically healthy obesity and metabolically unhealthy obesity

Ying CUI ; Zejiaxin NIU ; Yang WANG

Chinese Journal of Arteriosclerosis.2025;33(9):737-744. doi:10.20039/j.cnki.1007-3949.2025.09.001

Obesity has been recognized by the World Health Organization(WHO)as a global public health issue and is closely associated with an increased risk of metabolic diseases such as type 2 diabetes,hypertension,dyslipidemia,and cardiovascular disease(CVD).Based on the presence or absence of metabolic abnormalities,obese individuals can be categorized into metabolically healthy obesity(MHO)and metabolically unhealthy obesity(MUO).This review aims to explore the significant differences between MHO and MUO individuals in terms of pathophysiological mechanisms,clini-cal characteristics,and cardiovascular disease risk.Compared to those with MHO,MUO individuals exhibit more pro-nounced insulin resistance,persistent state of inflammation,and ectopic lipid accumulation,resulting in a higher risk of CVD and necessitating active and effective interventions.Furthermore,growing evidence suggests that MHO is not a stable long-term metabolic condition but may transition to MUO;hence,its long-term CVD risk should not be overlooked.This article also discusses the potential mechanisms underlying metabolic heterogeneity in MHO and MUO,including the regulation of adipose tissue distribution and function by genetic and environmental factors,as well as the potential role of li-festyle interventions in improving metabolic health.Future research should further investigate the pathophysiological basis of MHO and MUO to facilitate early identification of obesity-related CVD risk and develop effective prevention and treatment strategies.

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Research progress on HIIT intervention in improving vascular endothelial function in obese children and adolescents

Fucheng SUN ; Meng ZHAO ; Ye XU ; Limeixuan HAN ; Tianfeng YAO

Chinese Journal of Arteriosclerosis.2025;33(9):754-761,802. doi:10.20039/j.cnki.1007-3949.2025.09.003

Metabolic diseases such as childhood and adolescent obesity,type 2 diabetes have become urgent public health challenges that need to be addressed.Endothelial dysfunction is considered as a precursor event of cardiovascular disease,and its prevention and treatment have become an essential focus of health management.Being obese and spend-ing less time exercising in children and adolescents almost exist simultaneously.In this context,time-saving high-intensity interval training(HIIT)intervention is essential to prevent cardiovascular and cerebrovascular diseases in children and adolescents.This article aims to comprehensively review the latest research progress on HIIT intervention in improving vascular endothelial function in obese children and adolescents.Through systematic review and comprehensive analysis,it provides theoretical and practical guidance for future research and promotes the development and implementation of effective health interventions.

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piRNA-823 inhibits high glucose induced endothelial-mesenchymal transition and an-giogenesis in human umbilical vein endothelial cells through TGF-β1/Smad2/3 signa-ling pathway

Yang HAN ; Jianning QIN ; Yao TAN ; Letian YU ; Shunlin QU

Chinese Journal of Arteriosclerosis.2025;33(9):762-771. doi:10.20039/j.cnki.1007-3949.2025.09.004

Aim To investigate the biological function and molecular mechanisms of piRNA-823 in the phenotypic transformation of human umbilical vein endothelial cells(HUVEC)induced by high glucose.Methods HUVEC were incubated in high glucose(33.3 mmol/L)culture medium for 72 h.The relative expression levels of piR-NA-823 were detected by RT-qPCR,the expression changes of endothelial cell markers,mesenchymal cell markers and proteins related to transforming growth factor-β1(TGF-β1)signaling pathway were detected by Western blot,the changes of cell migration ability were evaluated by scratch and Transwell assays,the formation of new angiogenesis were assessed through angiogenesis experiments.piRNA-823 mimic(overexpression of piRNA-823)were transfected into HUVEC to analyze their effects on high glucose induced endothelial-mesenchymal transition(EndMT)and angiogenesis.Further in-tervention was performed using TGF-β1 activator(SRI011381)and inhibitor(SB525334)to verify whether piRNA-823 ex-erts its effect by regulating the TGF-β1/Smad2/3 signaling pathway.Results piRNA-823 mimic significantly inhibited the viability,proliferation,migration and angiogenesis of HUVEC induced by high glucose.The piRNA-823 mimic inhibited high glucose induced EndMT in HUVEC,characterized by upregulation of endothelial cell markers and downregulation of mesenchymal cell markers.Scratch experiments,Transwell experiments and angiogenesis experiments further confirmed that piRNA-823 mimic could effectively reverse high glucose induced HUVEC proliferation,migration a-bility enhancement,and increase in the number of new angiogenesis.Mechanistic studies revealed that the TGF-β1 acti-vator partially reversed the protective effect of piRNA-823 mimic,whereas the TGF-β1 inhibitor enhanced its effect,sug-gesting that piRNA-823 exerts its regulatory role by suppressing the activation of the TGF-β1/Smad2/3 signaling pathway.Conclusion piRNA-823 significantly inhibits high glucose induced EndMT,proliferation,migration and angiogenesis in HUVEC by suppressing the activation of TGF-β1/Smad2/3 signaling pathway.

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Empagliflozin alleviates ox-LDL-induced injury of human umbilical vein endothelial cells by inhibiting the EGFR signaling pathway

Jiangtao LI ; Debao ZHANG ; Junyu CHEN ; Xiao KE ; Yulang HUANG

Chinese Journal of Arteriosclerosis.2025;33(9):772-780. doi:10.20039/j.cnki.1007-3949.2025.09.005

Aim To investigate the protective and reparative effect of empagliflozin on oxidized-low density lipo-protein(ox-LDL)-induced injury in human umbilical vein endothelial cells(HUVEC)and its mechanism of action.Methods Primary HUVEC were cultured in vitro.ox-LDL was used to induce HUVEC injury model,and the cell sur-vival rate was measured by CCK-8 assay.EDU method was used to detect cell proliferation.Western blot was used to detect the protein levels of Ki-67,Bcl-2,cleaved Caspase-3,Bax,endothelial nitric oxide synthase(eNOS),intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule 1(VCAM-1)and epidermal growth factor receptor(EGFR)in HUVEC.RT-qPCR was used to detect the mRNA expression levels of interleukin-6(IL-6)and tumor necro-sis factor-α(TNF-α)in HUVEC.Using Swiss targets,GeneCards databases,gene ontology(GO)and Kyoto encyclope-dia of genes and genomes(KEGG),protein-protein interaction(PPI)network analysis,and ClickDocking(https://mcule.com/apps/1-click-docking/)to predict the target of empagliflozin.Results CCK-8 results showed that 0.025 μmol/L empagliflozin significantly alleviated ox-LDL-induced HUVEC injury(P＜0.01).EDU results showed that ox-LDL treatment for 24 h significantly inhibited the proliferation of HUVEC(P＜0.01),while empagliflozin treatment sig-nificantly alleviated the inhibition of cell proliferation(P＜0.01).The results of Western blot showed ox-LDL treatment significantly decreased the protein expression levels of Ki-67,Bcl-2,and eNOS,and increased the protein expression levels ofcleaved Caspase-3,Bax,ICAM-1,and VCAM-1 in HUVEC(all P＜0.05).However,empagliflozin treatment reversed these changes(all P＜0.05).RT-qPCR results showed that ox-LDL treatment increased the mRNA expression levels of IL-6 and TNF-α in HUVEC(P＜0.01),while empagliflozin treatment decreased their expression levels(P＜0.05).However,after adding EGFR agonist NSC 228155,the protective effect of empagliflozin against ox-LDL-mediated HUVEC injury was significantly reversed(P＜0.05).Conclusion Empagliflozin can significantly reduce ox-LDL-in-duced HUVEC injury,which may be related to EGFR signaling pathway.

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Serum Gal-3,sST2,ProDH levels and their clinical significance in elderly patients with heart failure

Yapeng LI

Chinese Journal of Arteriosclerosis.2025;33(9):781-788. doi:10.20039/j.cnki.1007-3949.2025.09.006

Aim To investigate the levels and clinical significance of serum galectin-3(Gal-3),soluble sup-pression of tumorigenicity 2(sST2)and proline dehydrogenase(ProDH)in elderly patients with heart failure.Meth-ods Using a single-center retrospective cohort study design,165 elderly patients with heart failure who were diagnosed and treated in our hospital from January 2022 to October 2023 were selected as the observation group,and 120 elderly patients with normal cardiac function and no heart disease who underwent physical examination in our hospital during the same peri-od were selected as the control group.Serum Gal-3,sST2,and ProDH levels were compared between the two groups.The ROC curve was drawn to analyze the diagnostic value of Gal-3,sST2 and ProDH levels in elderly patients with heart failure.Spearman rank correlation was used to analyze the correlation between Gal-3,sST2,ProDH and heart failure in the elderly.At the same time,the observation group was divided into a poor prognosis group(n=49)and a good progno-sis group(n=116)according to the prognosis.The general data of the two groups were compared.The associated risk factors influencing the poor prognosis of elderly heart failure were examined using Logistic regression model.ROC curve was created to examine the predictive value of associated risk factors for a poor prognosis of elderly heart failure.Re-sults The levels of Gal-3 and sST2 were significantly higher in observation group than those in control group,the level of ProDH was significantly lower than in control group,with statistical significance(P＜0.05).ROC curve results showed that Gal-3,sST2,ProDH and combined diagnosis were statistically significant for the diagnosis of heart failure in the elder-ly(P＜0.05).The AUC of the combined diagnosis was 0.996,95％CI was 0.992～1.000,the sensitivity was 0.970,the specificity was 0.975,and the diagnostic value was higher.Spearman rank correlation analysis showed that Gal-3 and sST2 were positively correlated with heart failure in the elderly(P＜0.05),and ProDH was negatively correlated with heart failure in the elderly(P＜0.05).Multivariate analysis of Logistic regression model showed that NYHA cardiac function grade IV,high level of Gal-3 and high level of sST2 were independent risk factors for poor prognosis of elderly patients with heart failure(P＜0.05),and elevated left ventricular ejection fraction(LVEF)and high level of ProDH were protective factors(P＜0.05).ROC curve results showed that NYHA cardiac function classification,LVEF,Gal-3,sST2,ProDH and combined prediction were statistically significant in predicting the poor prognosis of elderly heart failure(P＜0.05).The AUC of combined prediction was 0.983,95％CI was 0.969～0.998,the sensitivity was 0.939,the specificity was 0.948,and the predictive value was higher.Conclusion In this study,the combined predictive efficacy of Gal-3,sST2 and ProDH was systematically analyzed in elderly patients with heart failure for the first time,and it was found that the combination of the three had significant clinical value in diagnosis and prognosis evaluation.NYHA cardiac function grade Ⅳ,high level of Gal-3 and high level of sST2 were independent risk factors for poor prognosis of elderly patients with heart failure.Elevated LVEF and high level of ProDH were protective factors,all of which have certain predictive value,and the combined predictive value is higher.

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Mechanisms and Prospects of EGCG in the Prevention and Treatment of Atheroscle-rosis

Xueqi DAI ; Guanjie ZHANG ; Jing LI ; Huiyu LONG ; Hui SUN

Chinese Journal of Arteriosclerosis.2025;33(9):803-809. doi:10.20039/j.cnki.1007-3949.2025.09.009

Atherosclerosis(As)is a chronic inflammatory vascular disease and serves as the pathological basis for various cardiovascular diseases.Epigallocatechin-3-O-gallate(EGCG)is the most abundant and biologically active com-pound in green tea,possessing multiple pharmacological effects such as anti-inflammatory,antiviral,and antioxidative stress properties.In recent years,studies have found that EGCG can regulate lipid metabolism,improve vascular endo-thelial function,and enhance plaque stability,demonstrating its potential value in combating As.This article provides a systematic review of the mechanisms underlying EGCG's anti-As effects,aiming to offer multi-faceted theoretical support for its further research and clinical application in the prevention and treatment of As.

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Fungal species distribution and susceptibility factors analysis of secondary pulmonary fungal infections in patients with coronary heart disease combined with COPD

Ning LI ; Meimei AI

Chinese Journal of Arteriosclerosis.2025;33(9):789-794. doi:10.20039/j.cnki.1007-3949.2025.09.007

Aim To investigate fungal species distribution and associated susceptibility factors of secondary pul-monary fungal infections in patients with coronary heart disease(CHD)combined with chronic obstructive pulmonary dis-ease(COPD).Methods A total of 68 patients with CHD combined with COPD who developed secondary pulmonary fungal infections were retrospectively selected from those admitted to our hospital from March 2021 to June 2024 as the in-fected group,and the diagnosis was confirmed by pathogenic identification of qualified sputum specimens and alveolar lav-age fluid,while 68 patients with simple CHD combined with COPD were randomly included in the ratio of 1∶1,and were set up as the uninfected group.Clinical data of patients in both groups were collected,Logistic regression model was used to analyze the susceptible factors of secondary pulmonary fungal infection in patients with CHD combined with COPD.The receiver operating characteristic(ROC)curve was used to assess the diagnostic efficacy and accuracy of predictive indica-tors.Results In 68 patients with CHD combined with COPD secondary to pulmonary fungal infections,76 strains of fungi were detected,including 48 strains of Candida albicans(63.16％).Multivariate Logistic regression analysis re-vealed that hospital days(OR=0.160),duration of antibiotic use(OR=0.221),invasive operations(OR=0.248),combined hypoproteinemia(OR=0.104),combined diabetes mellitus(OR=0.269),and combined pulmonary tuberculosis(OR=0.199)were the susceptible factors for secondary pulmonary fungal infection in patients with CHD com-bined with COPD(P＜0.05).The results of the ROC curve showed that the area under the curve(AUC)of hospital days,combined hypoproteinemia,combined diabetes and combined detection for evaluating pulmonary fungal infection in patients with CHD combined with COPD were 0.610(95％CI:0.515～0.705),0.647(95％CI:0.554～0.740,0.603(95％CI:0.508～0.698)and 0.843(95％CI:0.776～0.911),respectively,which were all statistically significant compared with the area covered under the ROC curve of 0.5(P＜0.05).Conclusion The pathogen of secondary pul-monary fungal infection is mainly Candida albicans in patients with CHD combined with COPD.Hospital days,duration of antibiotics,invasive operations,combined hypoproteinemia,combined diabetes mellitus,and combined pulmonary tu-berculosis were risk factors of secondary pulmonary fungal infection in patients with CHD combined with COPD.

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