Cardiovascular Toxicology最新文献

{"title":"The potential Role of CYP2D6*10(c.100 C>T) Gene Polymorphism in Kidney Injury of Patients with Hypertension Complicated with Non-Elevated Cystatin C.","authors":"Yufeng Jiang, Kuangyi Wang, Xiaofei Mei, Yafeng Zhou","doi":"10.1007/s12012-024-09880-3","DOIUrl":"10.1007/s12012-024-09880-3","url":null,"abstract":"<p><p>This study aims to investigate the potential role of CYP2D6*10 (c.100 C>T) gene polymorphism in renal function injury among hypertensive patients without elevated cystatin C. A cohort of hypertensive patients without elevated cystatin C was enrolled between 2021 and 2024 in the Fourth Affiliated Hospital of Soochow University, and their peripheral venous blood was used for total RNA extraction and CYP2D6*10 genotype analysis. Based on kidney injury status, patients were categorized into two groups, hypertensive patients with kidney injury (n = 94) and those without (n = 893). General characteristics such as age, gender and hyperlipemia were compared between the two groups. Multiple genotype models were investigated between the two groups, including allele models, dominant models, recessive models, co-dominant models, and super-dominant models. The results revealed that in the co-dominant gene model (CC vs. CT vs. TT), the risk of hypertension combined with renal injury was lower with the CT genotype compared to the CC genotype (Odds Ratio (OR) = 0.55, 95% Confidence Interval (CI) = 0.32-0.93, p = 0.02). In the overdominance model (CC + TT vs. CT), the risk of hypertension and renal injury in CC and CT genotypes was 0.42 times lower than that in the CT genotype (OR = 0.42, 95% CI = 0.27-0.64, p < 0.001). This study proposes CYP2D610 gene polymorphism as a potential predictor of renal function injury in hypertensive patients with normal cystatin C levels.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"836-841"},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Molecular Mechanism of Radix Paeoniae Rubra.-Cortex Moutan. Herb Pair in the Treatment of Atherosclerosis: A Work Based on Network Pharmacology and In Vitro Experiments.","authors":"Caojian Zuo, Lidong Cai, Ya Li, Chencheng Ding, Guiying Liu, Changmei Zhang, Hexiang Wang, Yang Zhang, Mingyue Ji","doi":"10.1007/s12012-024-09881-2","DOIUrl":"10.1007/s12012-024-09881-2","url":null,"abstract":"<p><p>Radix Paeoniae Rubra. (Chishao, RPR) and Cortex Moutan. (Mudanpi, CM) are a pair of traditional Chinese medicines that play an important role in the treatment of atherosclerosis (AS). The main objective of this study was to identify potential synergetic function and underlying mechanisms of RPR-CM in the treatment of AS. The main active ingredients, targets of RPR-CM and AS-related genes were obtained from public databases. A Venn diagram was utilized to screen the common targets of RPR-CM in treating AS. The protein-protein interaction network was established based on STRING database. Biological functions and pathways of potential targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Cytoscape was used to construct the drug-compound-target-signal pathway network. Molecular docking was performed to verify the binding ability of the bioactive ingredients and the target proteins. The endothelial inflammation model was constructed with human umbilical vein endothelial cells stimulated with ox-LDL, and the function of RPR-CM in treating AS was verified by CCK-8 assay, enzyme-linked immunosorbent assay, and qPCR. In this study, 12 active components and 401 potential target genes of RPR-CM were identified, among which quercetin, kaempferol and baicalein were considered to be the main active components. A total of 1903 AS-related genes were identified through public databases and four GEO datasets (GSE57691, GSE72633, GSE6088 and GSE199819). There are 113 common target genes of RPR-CM in treating AS. PPI network analysis identified 17 genes in cluster 1 as the core targets. Bioinformatics analysis showed that RPR-CM in AS treatment was associated with multiple downstream biological processes and signal pathways. PTGS2, JUN, CASP3, TNF, IL1B, IL6, FOS, STAT1 were identified as the core targets of RPR-CM, and molecular docking showed that the main bioactive components of RPR-CM had good binding ability with the core targets. RPR-CM extract significantly inhibited the levels of inflammatory factors TNF-α, IL-6, IL-1β, MCP-1, VCAM-1 and ICAM-1 in HUVECs, and inhibited endothelial inflammation. This study revealed the active ingredients of RPR-CM, and identified the key downstream targets and signaling pathways in the treatment of AS, providing theoretical basis for the application of RPR-CM in prevention and treatment of AS.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"800-817"},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marein Alleviates Doxorubicin-Induced Cardiotoxicity through FAK/AKT Pathway Modulation while Potentiating its Anticancer Activity.","authors":"Juanjuan Xu, Manjun Lv, Xiaohong Ni","doi":"10.1007/s12012-024-09882-1","DOIUrl":"10.1007/s12012-024-09882-1","url":null,"abstract":"<p><p>Doxorubicin (DOX) is an effective anticancer agent, yet its clinical utility is hampered by dose-dependent cardiotoxicity. This study explores the cardioprotective potential of Marein (Mar) against DOX-induced cardiac injury and elucidates underlying molecular mechanisms. Neonatal rat cardiomyocytes (NRCMs) and murine models were employed to assess the impact of Mar on DOX-induced cardiotoxicity (DIC). In vitro, cell viability, oxidative stress were evaluated. In vivo, a chronic injection method was employed to induce a DIC mouse model, followed by eight weeks of Mar treatment. Cardiac function, histopathology, and markers of cardiotoxicity were assessed. In vitro, Mar treatment demonstrated significant cardioprotective effects in vivo, as evidenced by improved cardiac function and reduced indicators of cardiac damage. Mechanistically, Mar reduced inflammation, oxidative stress, and apoptosis in cardiomyocytes, potentially via activation of the Focal Adhesion Kinase (FAK)/AKT pathway. Mar also exhibited an anti-ferroptosis effect. Interestingly, Mar did not compromise DOX's efficacy in cancer cells, suggesting a dual benefit in onco-cardiology. Molecular docking studies suggested a potential interaction between Mar and FAK. This study demonstrates Mar's potential as a mitigator of DOX-induced cardiotoxicity, offering a translational perspective on its clinical application. By activating the FAK/AKT pathway, Mar exerts protective effects against DOX-induced cardiomyocyte damage, highlighting its promise in onco-cardiology. Further research is warranted to validate these findings and advance Mar as a potential adjunctive therapy in cancer treatment.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"818-835"},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicles in Cardiovascular Pathophysiology: Communications, Biomarkers, and Therapeutic Potential.","authors":"Zhe Cui, Ling Zhang, Guangyu Hu, Fuyang Zhang","doi":"10.1007/s12012-024-09875-0","DOIUrl":"10.1007/s12012-024-09875-0","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are diverse, membrane-bound vesicles released from cells into the extracellular environment. They originate from either endosomes or the cell membrane and typically include exosomes and microvesicles. These EVs serve as crucial mediators of intercellular communication, carrying a variety of contents such as nucleic acids, proteins, and lipids, which regulate the physiological and pathological processes of target cells. Moreover, the molecular cargo of EVs can reflect critical information about the originating cells, making them potential biomarkers for the diagnosis and prognosis of diseases. Over the past decade, the role of EVs as key communicators between cell types in cardiovascular physiology and pathology has gained increasing recognition. EVs from different cellular sources, or from the same source under different cellular conditions, can have distinct impacts on the management, diagnosis, and prognosis of cardiovascular diseases. Furthermore, it is essential to consider the influence of cardiovascular-derived EVs on the metabolism of peripheral organs. This review aims to summarize recent advancements in the field of cardiovascular research with respect to the roles and implications of EVs. Our goal is to provide new insights and directions for the early prevention and treatment of cardiovascular diseases, with an emphasis on the therapeutic potential and diagnostic value of EVs.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"711-726"},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterocyclic Amines Disrupt Lipid Homeostasis in Cryopreserved Human Hepatocytes.","authors":"Kennedy M Walls, Jonathan Y Joh, Kyung U Hong, David W Hein","doi":"10.1007/s12012-024-09874-1","DOIUrl":"10.1007/s12012-024-09874-1","url":null,"abstract":"<p><p>Metabolic dysfunction associated-steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH) is the liver manifestation of metabolic syndrome, which is characterized by insulin resistance, hyperglycemia, hypertension, dyslipidemia, and/or obesity. Environmental pollutant exposure has been recently identified as a risk factor for developing MASH. Heterocyclic amines (HCAs) are mutagens generated when cooking meat at high temperatures or until well-done. Recent epidemiological studies reported that dietary HCA exposure may be linked to insulin resistance and type II diabetes, and we recently reported that HCAs induce insulin resistance and glucose production in human hepatocytes. However, no previous studies have examined the effects of HCAs on hepatic lipid homeostasis. In the present study, we assessed the effects of two common HCAs, MeIQx (2-amino-3, 8-dimethylimidazo [4, 5-f] quinoxaline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4, 5-b] pyridine), on lipid homeostasis in cryopreserved human hepatocytes. Exposure to a single concentration of 25 μM MeIQx or PhIP in human hepatocytes led to dysregulation of lipid homeostasis, typified by significant increases in lipid droplets and triglycerides. PhIP significantly increased expression of lipid droplet-associated genes, PNPLA3 and HSD17B13, and both HCAs significantly increased PLIN2. Exposure to MeIQx or PhIP also significantly increased expression of several key genes involved in lipid synthesis, transport and metabolism, including FASN, DGAT2, CPT1A, SCD, and CD36. Furthermore, both MeIQx and PhIP significantly increased intracellular cholesterol and decreased expression of PON1 which is involved in cholesterol efflux. Taken together, these results suggest that HCAs dysregulate lipid production, metabolism, and storage. The current study demonstrates, for the first time, that HCA exposure may lead to fat accumulation in hepatocytes, which may contribute to hepatic insulin resistance and MASH.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"747-756"},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11300155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Oleic Acid Protects from Arsenic-Induced Cardiac Hypertrophy via AMPK/FoxO/NFATc3 Pathway.","authors":"Jayeeta Samanta, Arunima Mondal, Srimoyee Saha, Santanu Chakraborty, Arunima Sengupta","doi":"10.1007/s12012-024-09883-0","DOIUrl":"10.1007/s12012-024-09883-0","url":null,"abstract":"","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"842"},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Smokeless Tobacco on Cardiovascular Disease Risk in a Nigerian Metropolitan City.","authors":"Nelson I Oguanobi, Chioli P Chijioke, Samuel I Ghasi, Nkoyo I Nubila, Obinna C Nwoke, Caleb C Okolo","doi":"10.1007/s12012-024-09862-5","DOIUrl":"10.1007/s12012-024-09862-5","url":null,"abstract":"<p><p>The use of smokeless tobacco products (STP) as a substitute for tobacco smoking is driving increasing consumption of these products especially in developing countries. The study sought to make comparison of cardiovascular risk profile between chronic STP users and suitably matched tobacco-naïve controls. This is a preliminary report from the cross sectional part of a two-arm prospective study of Smokeless Tobacco Products Composition and Exposure Outcome in Enugu metropolis, Nigeria. Consecutively recruited current Smokeless tobacco users, who had no history of cigarette smoking, aged 18 years and above, residing in selected communities in Enugu metropolis, Nigeria were recruited for the study from October 2022 to July 2023. Age and sex matched non-tobacco users from same localities as the study subjects served as controls. Written informed consent to participate in the study was obtained from all study participants. All participants were screened by the investigators, using the study case report forms, to obtain data on medical history, demographic, clinical, laboratory, and electrocardiographic evaluation. Data from 54 STP-users and 54 non-STP-users (mean age 56.58 ± 8.15 years) were analyzed. Anthropometric parameters were similar in both groups. Smokeless tobacco users had higher erect and supine blood pressure indices as well as greater postural drop in systolic blood pressure. The occurrence of diabetes mellitus (20.37% versus 5.56%) and hypertension (25.93%; 11.11%) was significantly higher in the STP-users than in the non-user population, (p = 0.02192 and 0.04751 respectively). Electrocardiographic evaluation showed significantly increased QTc and dispersions of P-wave, QRS and QT intervals as well as reduced PR interval in STP users. Electrocardiographic abnormalities observed in STP users include left ventricular hypertrophy, left atrial enlargement, ST-segment elevation, short PR interval and long QTc. Use of smokeless tobacco products is associated with increased risk burden of diabetes mellitus and hypertensive heart disease. Electrocardiographic findings linked to STP-use in this study are features consistent with arrhythmia, ventricular repolarization abnormality, myocardial hypertrophy and ischaemia, suggesting that smokeless tobacco products are not safe substitutes for tobacco smoking.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"727-736"},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiotoxicity of HER2-Targeted Drugs When Combined with Other Drugs: A Systematic and Meta-analysis of Randomized Controlled Trials.","authors":"Jiakun Liu, Zhengyuan Meng, Xv Yidan","doi":"10.1007/s12012-024-09876-z","DOIUrl":"10.1007/s12012-024-09876-z","url":null,"abstract":"<p><p>The development and use of HER2-targeted drugs has improved the prognosis of HER2-positive cancer patients. However, in addition to improved survival rates, treatment-induced adverse events and nontumor-related deaths have increased. We sought to assess the incidence of cardiovascular adverse events when HER2-targeted drugs are combined with other drugs. We systematically searched the literature on the cardiotoxicity of anti-HER2 drugs in electronic databases, including PubMed, Web of Science, Cochrane Library, OVID and CNKI, from their inception to April 2022. The Cochrane Collaboration's tool for assessing risk of bias and the Jadad scale were used to evaluate the risk of bias and quality of the studies, respectively. For each included trial, we calculated the incidence of cardiovascular adverse effects (CAEs) and 95% confidence intervals (95% CIs) and performed a meta-analysis using a random effects model (REM). The meta-analysis was performed using R 4.2.1. We included 41 randomized clinical trials (RCTs) in the meta-analysis, consisting of 56 groups and 31,934 patients. The meta-analysis revealed the following: (1) The incidence of cardiotoxicity in groups given monoclonal antibody treatment was 14% for single therapy (95% CI: 2-34%) and 10%, 11%, and 12% for adjuvant therapy combined with combined therapy (95% CI: 6-13%), chemotherapy (95% CI: 8-13%) and endocrine therapy (95% CI: 7-18%), respectively. However, in the groups treated with the antibody‒drug conjugates (ADCs), the percentage of patients treated with the combination therapy was 1% (95% CI: 0-2%) and 5% (95% CI: 4-7%), respectively, with a significant difference (P < 0.01). The heterogeneity among the included studies was significant (I² = 94%, p < 0.01). (2) When monoclonal antibodies were combined with chemotherapy, the incidence of cardiotoxicity under anthracycline-containing therapy (10.3%) was significantly greater than that under nonanthracycline-containing therapy (8.8%). (3) Significant differences were found between subgroups, except for the endocrine group versus some others, although this difference might result from the different inclusion criteria of the original trials. (1) When anti-HER2 drugs are administered in combination with anthracycline-containing chemotherapy, the incidence of cardiotoxicity is greater than with other drugs. (2) Safety benefits can be achieved by replacing traditional monoclonal antibodies with ADCs. The comprehensive use of these drugs necessitates collaboration between oncologists and cardiologists.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"757-765"},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin Alleviates LPS-Stimulated Myocardial Injury through Regulating ALOX5/PI3K/AKT Pathway in Sepsis","authors":"Fang Guan, Hongsen Du, Jike Li, He Ren, Aiqiao Dong","doi":"10.1007/s12012-024-09901-1","DOIUrl":"https://doi.org/10.1007/s12012-024-09901-1","url":null,"abstract":"<p>Quercetin (QUE) has been found to inhibit the progression of sepsis-related diseases, including sepsis-induced cardiomyopathy (SIC). More information about the role and mechanism of QUE in SIC progression deserves further exploration. Human cardiomyocytes (AC16) were induced with LPS to mimic SIC cell models. Cell proliferation and apoptosis were determined using CCK8 assay, EdU assay, and flow cytometry. Cell inflammation and ferroptosis were evaluated by detecting IL-1β, TNF-α, Fe²⁺, ROS, GSH, and GPX4 levels. 5-lipoxygenase (ALOX5) expression was examined by quantitative real-time PCR and western blot. LPS treatment reduced AC16 cell proliferation, while enhanced apoptosis, inflammation, and ferroptosis. QUE repressed LPS-induced AC16 cell apoptosis, inflammation, and ferroptosis. ALOX5 was upregulated in SIC patients, and its expression was reduced by QUE. ALOX5 knockdown restrained LPS-induced apoptosis, inflammation, and ferroptosis in AC16 cells. The inhibitory effect of QUE on LPS-induced myocardial injury could be reversed by ALOX5 overexpression. QUE promoted the activity of PI3K/AKT pathway by reducing ALOX5 expression. QUE could alleviate LPS-induced myocardial injury by regulating ALOX5/PI3K/AKT pathway, suggesting that QUE might be used for treating SIC.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"34 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141775833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circ_0002331 Interacts with ELAVL1 to Improve ox-LDL-Induced Vascular Endothelial Cell Dysfunction via Regulating CCND2 mRNA Stability.","authors":"Feng Chen, Xiufeng Yu","doi":"10.1007/s12012-024-09865-2","DOIUrl":"10.1007/s12012-024-09865-2","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) have been discovered to serve as vital regulators in atherosclerosis (AS). However, the role and mechanism of circ_0002331 in AS process are still unclear. Human umbilical vein endothelial cells (HUVECs) were treated with ox-LDL to establish an in vitro model for AS. The expression levels of circ_0002331, Cyclin D2 (CCND2) and ELAVL1 were analyzed by quantitative real-time PCR. Cell proliferation, apoptosis, migration, invasion and angiogenesis were assessed by EdU assay, flow cytometry, transwell assay and tube formation assay. The protein levels of CCND2, ELAVL1, and autophagy-related markers were detected using western blot analysis. IL-8 level was analyzed by ELISA. The relationship between ELAVL1 and circ_0002331 or CCND2 was analyzed by RIP assay and RNA pull-down assay. Moreover, FISH assay was used to analyze the co-localization of ELAVL1 and CCND2 in HUVECs. Our data showed that circ_0002331 was obviously downregulated in AS patients and ox-LDL-induced HUVECs. Overexpression of circ_0002331 could promote proliferation, migration, invasion and angiogenesis, while inhibit apoptosis, autophagy and inflammation in ox-LDL-induced HUVECs. Furthermore, CCND2 was positively regulated by circ_0002331, and circ_0002331 could bind with ELAVL1 to promote CCND2 mRNA stability. Besides, CCND2 overexpression suppressed ox-LDL-induced HUVECs dysfunction, and its knockdown also reversed the regulation of circ_0002331 on ox-LDL-induced HUVECs dysfunction. In conclusion, circ_0002331 might be a potential target for AS treatment, which could improve ox-LDL-induced dysfunction of HUVECs via regulating CCND2 by binding with ELAVL1.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"625-636"},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}