Cardiovascular Drugs and Therapy最新文献

{"title":"DTX1 Regulates Aortic Dissection Progression by Modulating Vascular Smooth Muscle Cell Phenotypic Switching via Ubiquitination of ITGA5.","authors":"Dong Wang, Lingbo Yang, Junqing Zong","doi":"10.1007/s10557-026-07877-4","DOIUrl":"https://doi.org/10.1007/s10557-026-07877-4","url":null,"abstract":"<p><strong>Background: </strong>Aortic dissection (AD) is a life-threatening vascular disorder characterized by medial degeneration and phenotypic switching of vascular smooth muscle cells (VSMCs). While integrin subunit alpha 5 (ITGA5) has been implicated in VSMC plasticity, the upstream molecular mechanisms governing its regulation remain poorly defined.</p><p><strong>Methods: </strong>Publicly available transcriptomic datasets were analyzed using differential expression analysis and WGCNA to identify hub genes associated with AD. The UbiBrowser database was employed to predict potential E3 ubiquitin ligases targeting ITGA5. In vitro, human aortic smooth muscle cells (HASMCs) were stimulated with Angiotensin II to mimic pathological conditions, and subjected to gain and loss-of-function assays, protein stability analysis, and co-immunoprecipitation in combination with HEK-293T cells. A BAPN-induced AD mouse model was utilized to evaluate the in vivo studies. Protein and gene expression were assessed by Western blotting, qPCR, and immunofluorescence.</p><p><strong>Results: </strong>ITGA5 promoted the phenotypic switch of HASMCs toward a synthetic/inflammatory state. Deltex E3 ubiquitin ligase 1 (DTX1) directly interacted with ITGA5 and promoted its ubiquitination at lysine 137, leading to proteasome-dependent degradation. DTX1 overexpression suppressed ITGA5 levels, maintained contractile marker expression, and inhibited the synthetic/inflammatory phenotype of HASMCs. In vivo, DTX1 expression was downregulated and ITGA5 upregulated in BAPN-treated aortas, whereas DTX1 overexpression reduced ITGA5 levels, preserved medial integrity, and attenuated AD progression.</p><p><strong>Conclusion: </strong>This study identifies DTX1 as a novel E3 ubiquitin ligase that promotes ITGA5 degradation, thereby maintaining the contractile phenotype of VSMCs and limiting AD progression. Targeting the DTX1-ITGA5 axis may offer a promising therapeutic approach for AD.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834343","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":"NR1D2 Knockdown Alleviates Myocardial Infarction through Nrf2 Signaling Pathway Activation.","authors":"Ting Wang, Helong Xiao, Meijian Yang, Jing Liu, Yang Yang","doi":"10.1007/s10557-026-07879-2","DOIUrl":"https://doi.org/10.1007/s10557-026-07879-2","url":null,"abstract":"<p><strong>Purpose: </strong>Ferroptosis contributes to myocardial infarction (MI) pathogenesis. However, the role of nuclear receptor subfamily 1 group D member 2 (NR1D2) in MI-associated ferroptosis and its potential interaction with nuclear factor erythroid 2-related factor 2 (Nrf2) pathway remains unclear. We sought to determine whether NR1D2 regulates ferroptosis in MI through the Nrf2 pathway and to evaluate the therapeutic potential of NR1D2 knockdown.</p><p><strong>Methods: </strong>Bioinformatic analyses of GEO datasets identified NR1D2 as a key ferroptosis-related gene in MI. In vitro, NR1D2 expression was silenced in HL-1 cardiomyocytes subjected to hypoxia/reoxygenation (H/R) injury. Nrf2 inhibitor ML385 was used to verify pathway involvement. A mouse model of MI was established, and cardiac function was assessed following NR1D2 knockdown with or without ML385 co-treatment.</p><p><strong>Results: </strong>NR1D2 expression was significantly upregulated in MI. Its knockdown in H/R-injured cardiomyocytes reduced cell death, inflammation, and ferroptosis, as indicated by decreased Fe²⁺ and malondialdehyde levels and elevated GSH/GSSG ratio. These protective effects were abolished by ML385, confirming Nrf2 dependence. Mechanistically, NR1D2 knockdown activated the Nrf2/HO-1 signaling axis, leading to the upregulation of downstream effectors glutathione peroxidase 4and SLC7A11. In MI mice, NR1D2 knockdown improved cardiac function (increased EF and FS), decreased infarct size, and inhibited ferroptosis-effects that were also negated by ML385.</p><p><strong>Conclusion: </strong>NR1D2 aggravates MI injury by suppressing the Nrf2 pathway and promoting ferroptosis. Targeting NR1D2 activates Nrf2 signaling and alleviates ferroptotic damage, revealing a novel regulatory mechanism and identifying NR1D2 as a promising therapeutic target for MI.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811493","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":"Sources of Heterogeneity in the Efficacy of Statins for Primary Prevention of Cardiovascular Diseases: A Systematic Review with Meta-Regression and Meta-Analysis of Within-Study Subgroup Differences.","authors":"Yujun Long, Jianzhao Liu, Jiaxin Cai, Qiongqi Zhuang, Ting Cai, Junwen Zhou, Sanbao Chai, Tengfei Lin, Zhirong Yang","doi":"10.1007/s10557-026-07883-6","DOIUrl":"https://doi.org/10.1007/s10557-026-07883-6","url":null,"abstract":"<p><strong>Purpose: </strong>Evidence regarding sources of heterogeneity in the efficacy of statins for primary prevention of cardiovascular disease (CVD) remains limited. This study aimed to identify trial-level factors contributing to such heterogeneity.</p><p><strong>Methods: </strong>Relevant studies were systematically identified from a previous systematic review and through searches in PubMed, Embase, and Cochrane up to 20 January 2026. The protocol was registered in PROSPERO (CRD42024579932). Randomized controlled trials (RCTs) in adults without prior CVD that investigated statin treatment were included. Risk of bias was assessed using the Cochrane Risk of Bias tool. Meta-analyses were conducted to pool risk ratios (RRs) and 95% confidence intervals (CIs) for major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, and cardiovascular death. Univariate meta-regression analyses were conducted to assess the impact of trial-level covariates on the effect sizes, expressed as the ratio of risk ratios (RRR). Within-study subgroup differences were meta-analyzed by pooling ratio of effect sizes. Meta-regression analyses were conducted using complete-case trial-level data.</p><p><strong>Results: </strong>25 RCTs (102,667 participants) were included. Compared to no statin treatment, statin treatment was associated with a reduced risk of MACE (RR, 0.73[95% CI, 0.67 to 0.80], P < 0.001), MI (RR, 0.68[95% CI, 0.60 to 0.77], P < 0.001), stroke (RR, 0.76[95% CI, 0.65 to 0.89], P = 0.001) and cardiovascular death (RR, 0.81[95% CI, 0.71 to 0.95], P = 0.008). Univariate meta-regression indicated that higher baseline total cholesterol (RRR, 1.29 [95% CI, 1.07 to 1.57], P = 0.008), higher low-density lipoprotein cholesterol (LDL-C) (RRR, 1.31 [95% CI, 1.07 to 1.62], P = 0.010), higher triglycerides (RRR, 1.81 [95% CI, 1.17 to 2.81], P = 0.008) and lower statin intensity (RRR, 0.74 [95% CI, 0.59 to 0.94], P = 0.015) were significantly associated with reduced efficacy of statins for stroke prevention at the trial level.</p><p><strong>Conclusions: </strong>Statin therapy demonstrated consistent efficacy in CVD prevention across diverse populations, except that baseline lipid profiles and statin intensity may represent exploratory, hypothesis-generating signals of potential effect modification for stroke prevention, warranting further investigation.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811438","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 Single Antiplatelet, Dual Antiplatelet, and Anticoagulation Plus Antiplatelet Therapy on Branch Vessel Patency and Bleeding Risk Following Branched Endovascular Aortic Repair.","authors":"Lu Ye, Longbao Zhao, Xiaoling Xie, Juanping Zhang, Long Yang","doi":"10.1007/s10557-026-07886-3","DOIUrl":"https://doi.org/10.1007/s10557-026-07886-3","url":null,"abstract":"<p><strong>Purpose: </strong>To compare the effects of single antiplatelet (SAPT), dual antiplatelet (DAPT), and anticoagulation plus antiplatelet (AC + AP) therapies on branch vessel patency and bleeding risk after branched endovascular aortic repair (B-EVAR).</p><p><strong>Methods: </strong>This single-center retrospective cohort study included 250 patients with 880 target branches who underwent B-EVAR (2015-2025). Primary outcomes were branch patency loss (occlusion/stenosis requiring reintervention) and major bleeding (ISTH criteria). Propensity score weighting and competing risk regression controlled confounding.</p><p><strong>Results: </strong>During median 18-month follow-up, 82 branches (9.3%) lost patency: 12.0% (SAPT), 7.0% (DAPT), 7.5% (AC + AP). DAPT significantly improved patency vs. SAPT (sHR 0.72, p = 0.045). Major bleeding occurred in 22 patients (8.8%): 4.4% (SAPT), 7.5% (DAPT), 22.5% (AC + AP). AC + AP tripled bleeding risk (HR 3.10, p = 0.001); DAPT showed non-significant trend (HR 1.62, p = 0.13).</p><p><strong>Conclusion: </strong>DAPT provided the most favorable balance between branch vessel patency and major bleeding after B-EVAR. AC + AP was associated with substantially higher bleeding and should be reserved for patients with an independent indication for anticoagulation. Taken together with prior multicenter European and US consortium data, these findings support a class IB-level preference for DAPT in patients without competing anticoagulation needs; prospective randomized multicenter trials are needed to support a class IA recommendation.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811487","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":"ANRIL in Cardiovascular Diseases: Expression, Mechanism and Therapeutic Implications.","authors":"Hao Yang, Ying Li, Qiushuang Cai, Huimin Hua, Xia Liu, Yifei Liu, Wei Qin, Renfang Mao","doi":"10.1007/s10557-026-07884-5","DOIUrl":"https://doi.org/10.1007/s10557-026-07884-5","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) remain a leading cause of global mortality, with pathogenesis driven by multifactorial processes including genetic susceptibility, metabolic dysregulation, angiogenesis, and inflammation. Long non-coding RNAs (lncRNAs) have been recognized as key modulators of gene expression in cardiovascular pathophysiology. Among them, the Antisense Non-coding RNA in the INK4 Locus (ANRIL)-mapping to the well-established CVD-associated chromosome 9p21 locus-has garnered substantial research interest. Initially identified in melanoma, ANRIL spans approximately 126.3 kb and comprises 19 exons, existing in both linear and circular isoforms with distinct functional profiles. This review systematically outlines the dysregulation of ANRIL expression across seven major cardiovascular conditions and elucidates the isoform-specific mechanisms through which it contributes to disease progression, integrating recent advances in this field. We further discuss emerging evidence suggesting a potential role of ANRIL in cardiac hypertrophy. In light of its involvement in diverse cardiovascular disorders, ANRIL represents a compelling candidate for therapeutic target and a promising biomarker, warranting further translational investigation.</p>","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811455","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":"From Mechanism to Therapy: Establishing an Integrated Framework for the Regulation and Intervention of Matrix Vesicles in Vascular Calcification.","authors":"Mincheng Yu, Jingzheng Chen, Xinyue Wang, Ling Chen, Xiaomei Ren, Mayibai Mushajiang, Liqun Ren, Zhongqun Wang","doi":"10.1007/s10557-026-07881-8","DOIUrl":"https://doi.org/10.1007/s10557-026-07881-8","url":null,"abstract":"","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763323","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":"Molecular Mechanisms Underlying the Comorbidity of Type 2 Diabetes Mellitus and Coronary Artery Disease: from Insulin Resistance and Inflammation to Endothelial Dysfunction and Therapeutic Implications.","authors":"Min Zhong, Xin Wu, Yu Liu, Yirun Mao, Meng Liu, Xing Liu, Qin Liu","doi":"10.1007/s10557-026-07882-7","DOIUrl":"https://doi.org/10.1007/s10557-026-07882-7","url":null,"abstract":"","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763351","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":"Possible clinical drug interactions between ticagrelor and concomitant medications: for adverse drug event monitoring in real-world.","authors":"Tianya Liu, Zhuang Chen, Rui Wang, Xiaomei Xu, Fang Gao, Jie Zu, Zhiping Wang, Yiming Tian","doi":"10.1007/s10557-026-07871-w","DOIUrl":"https://doi.org/10.1007/s10557-026-07871-w","url":null,"abstract":"","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763329","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 Gut Microbiota-Metabolite-Host Axis in Cardiometabolic Diseases: Bridging Bench to Bedside.","authors":"Lang Chen, Di Yang","doi":"10.1007/s10557-026-07875-6","DOIUrl":"https://doi.org/10.1007/s10557-026-07875-6","url":null,"abstract":"","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697870","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":"Unmeasured Confounders and Control Group Heterogeneity in Laser-Assisted Lead Extraction.","authors":"Yinglei Lin","doi":"10.1007/s10557-026-07873-8","DOIUrl":"https://doi.org/10.1007/s10557-026-07873-8","url":null,"abstract":"","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697878","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}