Cardiovascular Research最新文献

{"title":"Cardiomyocyte SORBS2 expression increases in heart failure and regulates integrin interactions and extracellular matrix composition.","authors":"Louk T Timmer, Elvira den Hertog, Danielle Versteeg, Harm Post, Job A J Verdonschot, Jantine Monshouwer-Kloots, Eirini Kyriakopoulou, Ilaria Perini, Tim Koopmans, Petra van der Kraak, Lorena Zentilin, Stephane R B Heymans, Aryan Vink, Mauro Giacca, Albert J R Heck, Eva van Rooij","doi":"10.1093/cvr/cvaf021","DOIUrl":"10.1093/cvr/cvaf021","url":null,"abstract":"<p><strong>Aims: </strong>In this study, we aimed to uncover genes associated with stressed cardiomyocytes by combining single-cell transcriptomic data sets from failing cardiac tissue from both humans and mice.</p><p><strong>Methods and results: </strong>Our bioinformatic analysis identified SORBS2 as conserved NPPA-correlated gene. Using mouse models and cardiac tissue from human heart failure patients, we demonstrated that SORBS2 expression is consistently increased during pathological remodelling, correlates to disease severity, and is regulated by GATA4. By affinity purification mass spectrometry, we showed SORBS2 to interact with the integrin-cytoskeleton connections. Cardiomyocyte-specific genetic loss of Sorbs2 in adult mice changed integrin interactions, indicated by the increased expression of several integrins and altered extracellular matrix components connecting to these integrins, leading to an exacerbated fibrotic response during pathological remodelling.</p><p><strong>Conclusion: </strong>Sorbs2 is a cardiomyocyte-enriched gene that is increased during progression to heart failure in a GATA4-dependent manner and correlates to phenotypical hallmarks of cardiac failure. Our data indicate SORBS2 to function as a crucial regulator of integrin interactions and cardiac fibrosis.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"585-600"},"PeriodicalIF":10.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing cardiovascular risk assessment.","authors":"Christos P Kotanidis, Brittany Weber","doi":"10.1093/cvr/cvae234","DOIUrl":"10.1093/cvr/cvae234","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"523-525"},"PeriodicalIF":10.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The three calmodulin genes - territories defined?","authors":"Marcos Gonzalez,Quang-Kim Tran","doi":"10.1093/cvr/cvaf075","DOIUrl":"https://doi.org/10.1093/cvr/cvaf075","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"23 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist tirzepatide promotes branched chain amino acid catabolism to prevent myocardial infarction in non-diabetic mice.","authors":"Mengya Chen, Nan Zhao, Wenke Shi, Yun Xing, Shiqiang Liu, Xianxian Meng, Lanlan Li, Heng Zhang, Yanyan Meng, Saiyang Xie, Wei Deng","doi":"10.1093/cvr/cvaf005","DOIUrl":"10.1093/cvr/cvaf005","url":null,"abstract":"<p><strong>Aims: </strong>A novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, tirzepatide (LY3298176, TZP), has been developed to treat Type 2 diabetes mellitus (T2DM). In ischaemic heart diseases, TZP is involved in cardiac metabolic processes. However, its efficacy and safety in treating heart failure (HF) following myocardial infarction (MI) remain uncertain.</p><p><strong>Methods and results: </strong>Herein, 12 week C57BL/6J mice were subjected to MI surgery, followed by administration of TZP. The effects of TZP on cardiac function and metabolism were thoroughly assessed by physiological, histological, and cellular analyses. Downstream effectors of TZP were screened through untargeted metabolomics analysis and molecular docking. Construct a lower branched chain amino acid (BCAA) diet model to determine whether TZP's cardioprotective effect is associated with reducing BCAA levels. Our results demonstrated that TZP reduced mortality following MI, decreased the infarct area, and attenuated cardiomyocyte necrosis. Pathological evaluation of cardiac tissues demonstrated increased fibrosis repair and decreased inflammatory infiltration. Mechanistically, untargeted metabolomics analysis uncovered a positive correlation between TZP and the BCAA catabolism pathway. The molecular docking verified that TZP could bind with branched-chain keto acid dehydrogenase E1 subunit α (BCKDHA). TZP reduced BCKDHA phosphorylation at S293, enhanced BCAA catabolism, and inhibited the activation of metabolism by activating rapamycin (mTOR) signalling pathway. Furthermore, mice fed a low-BCAA diet post-MI demonstrated reduced cardiomyocyte necrosis, increased fibrosis repair, and decreased inflammatory infiltration. These cardioprotective effects were further enhanced when used synergistically with TZP.</p><p><strong>Conclusion: </strong>Taken together, our findings provide new perspectives on the unrecognized role of TZP in cardiac protection. TZP enhanced BCAA catabolism and attenuated BCAA/mTOR signalling pathway in MI mice. Consequently, this study may present novel therapeutic options for patients with HF.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"454-467"},"PeriodicalIF":10.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Down-regulation of histone deacetylase 2 attenuates ventricular arrhythmias in a mouse model of cardiac hypertrophy through up-regulation of Kv channel-interacting protein 2 expression.","authors":"Wenjuan Liu, Jianping Liu, Gang Wang, Wanwen Cheng, Haochen Gong, Yujuan Song, Ming Song, Yixin Zhuge, Ying Li, Jie Liu","doi":"10.1093/cvr/cvaf008","DOIUrl":"10.1093/cvr/cvaf008","url":null,"abstract":"<p><strong>Aims: </strong>Decrease in repolarizing K+ currents, particularly the fast component of transient outward K+ current (Ito,f), prolongs action potential duration (APD) and predisposes the heart to ventricular arrhythmia during cardiac hypertrophy. Histone deacetylases (HDACs) have been suggested to participate in the development of cardiac hypertrophy, and Class I HDAC inhibition has been found to attenuate pathological remodelling. This study investigated the potential therapeutic effects of HDAC2 on ventricular arrhythmia in pressure overload-induced cardiac hypertrophy.</p><p><strong>Methods and results: </strong>An in vivo cardiac hypertrophic model was produced by performing transverse aortic constriction (TAC) surgery and an in vitro cardiomyocyte hypertrophy model by stimulating neonatal rat ventricular myocytes (NRVMs) with phenylephrine (PE). HDAC2 expression was up-regulated in TAC mouse hearts and in PE-stimulated cardiomyocytes. Susceptibility to ventricular arrhythmia was increased in TAC mice, while Ito,f was decreased and APD was prolonged in TAC cardiomyocytes. Heart-specific knockdown (HKD) of HDAC2 by RNA interference increased Ito,f, shortened APD, and decreased susceptibility to ventricular arrhythmia. Concomitantly, HKD increased the expression of the obligatory β sub-unit of Ito,f, Kv channel-interacting protein 2 (KChIP2), which is down-regulated in hypertrophic hearts. The effects of HKD on KChIP2 expression, Ito,f and APD were also observed in PE-stimulated cardiomyocytes. Mechanistically, HKD increased H3K4me3 abundance and H3K4me3 enrichment at the Kcnip2 promoter in cardiomyocytes. HKD also decreased the expression of KDM5, the H3K4me3 demethylase, which resulted in H3K4me3 up-regulation. While investigating the regulatory mechanisms underlying the effect of HDAC2 on KDM5 stability, we identified CNOT4 as the active KDM5 ubiquitinase in cardiomyocytes. HKD increased CNOT4 expression and CNOT4-KDM5 interactions and thus enhanced the polyubiquitinated degradation of KDM5.</p><p><strong>Conclusion: </strong>HDAC2 inhibition serves as a novel therapeutic strategy for preventing cardiac hypertrophy-associated electrophysiological remodelling. Furthermore, we identified a novel signalling pathway of CNOT4-mediated KDM5 degradation contributing to the up-regulation of H3K4me3-mediated KChIP2 expression in response to HDAC2 inhibition.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"424-439"},"PeriodicalIF":10.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: SerpinB1 targeting safeguards against pathological cardiac hypertrophy and remodelling by suppressing cardiomyocyte pyroptosis and inflammation initiation.","authors":"","doi":"10.1093/cvr/cvaf002","DOIUrl":"10.1093/cvr/cvaf002","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"522"},"PeriodicalIF":10.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel approach to modelling acute cardiac decompensation in rats.","authors":"Arne Thiele, Hendrik Bartolomaeus, Harithaa Anandakumar, Nadine Haase, Arnd Heuser, Dominik N Müller, Ralf Dechend, Nicola Wilck","doi":"10.1093/cvr/cvae268","DOIUrl":"10.1093/cvr/cvae268","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"379-381"},"PeriodicalIF":10.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International partnership to nurture future cardiovascular research leaders in Europe.","authors":"Metin Avkiran","doi":"10.1093/cvr/cvae176","DOIUrl":"10.1093/cvr/cvae176","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"369-370"},"PeriodicalIF":10.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective effects of a 'twincretin' drug tirzepatide in heart failure following myocardial infarction.","authors":"Rui Shang, Brian Rodrigues","doi":"10.1093/cvr/cvaf006","DOIUrl":"10.1093/cvr/cvaf006","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"371-373"},"PeriodicalIF":10.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoring balance with recombinant interleukin-37: hope for halting chronic inflammation in calcific aortic valve disease.","authors":"Nalin H Dayawansa, Sara Baratchi, Karlheinz Peter","doi":"10.1093/cvr/cvaf018","DOIUrl":"10.1093/cvr/cvaf018","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"376-378"},"PeriodicalIF":10.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}