Cardiovascular Research最新文献

{"title":"Correction to: Patient-specific iPSC-derived cardiomyocytes reveal abnormal regulation of FGF16 in a familial atrial septal defect.","authors":"","doi":"10.1093/cvr/cvae227","DOIUrl":"10.1093/cvr/cvae227","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"2320"},"PeriodicalIF":10.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562650","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":"Epitranscriptomic regulation of cardiac fibrosis via YTHDF1-dependent PIEZO2 mRNA m6A modification.","authors":"Ji-Fei Ding, Bin Tu, Kai Song, Zhen-Yu Liu, Li-Chan Lin, Zhi-Yan Liu, Yan Shi, Jing-Jing Yang, Jian-Yuan Zhao, Hui Tao","doi":"10.1093/cvr/cvae239","DOIUrl":"10.1093/cvr/cvae239","url":null,"abstract":"<p><strong>Aims: </strong>Mechanosensitive (MS) ion channels play a key role in heart development, physiology, and disease. However, little is known about the molecular mechanisms of the MS non-selective cationic channel Piezo family in cardiac fibrosis.</p><p><strong>Methods and results: </strong>Mice were treated with ISO/Ang-II/TAC to induce cardiac fibrosis. AAV9 carrying POSTN promoter-driven small hairpin RNA targeting YTHDF1, and Piezo2 were administered to ISO mice to investigate their roles in cardiac fibrosis. RNA-seq, single-cell sequencing, and histological and biochemical analyses were performed to determine the mechanism by which YTHDF1 regulates Piezo2 expression in cardiac fibrosis. Piezo2 was reconstituted in YTHDF1-deficient cardiac fibroblasts (CFs) and mouse hearts to study its effects on CF autophagy and fibrosis. Piezo2 but not Piezo1 expression increased in experimental cardiac fibrosis and TGF-β1-induced CFs. Fibroblast-specific Piezo2 deficiency ameliorated fibroblast activation and autophagy and inhibited cardiac fibrosis. Mechanistically, Piezo2 up-regulation was associated with elevated m6A mRNA levels. Site-specific m6A modifications at peak_26355 were crucial for regulating the binding of YTHDF1 to Piezo2 mRNA and inducing Piezo2 translation. Notably, Piezo2 epitranscriptomic repression ameliorated experimental cardiac fibrosis.</p><p><strong>Conclusions: </strong>We demonstrated a novel epitranscriptomic mechanism through which YTHDF1 recognizes Piezo2 and controls cardiac fibroblast autophagy and fibrosis through m6A-dependent modulation. Our findings provide new insights for the development of preventive measures for cardiac fibrosis.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"2236-2248"},"PeriodicalIF":10.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582128","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":"TGF-β signalling: the Dr Jekyll and Mr Hyde of the aortic aneurysms.","authors":"Sara Perrotta, Daniela Carnevale, Giuseppe Lembo","doi":"10.1093/cvr/cvae245","DOIUrl":"10.1093/cvr/cvae245","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"2160-2162"},"PeriodicalIF":10.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675217","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":"Identifying optimal reference genes for real-time quantitative polymerase chain reaction in human myocardial tissues.","authors":"Maria Camacho-Encina, Laura K Booth, Rachael Redgrave, Minna Honkanen-Scott, William E Scott, Carmen Martin-Ruiz, Guy MacGowan, Sarah Richardson, John Dark, Simon Tual-Chalot, Gavin D Richardson","doi":"10.1093/cvr/cvae194","DOIUrl":"10.1093/cvr/cvae194","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"2163-2165"},"PeriodicalIF":10.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139417","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":"SGLT2 expression in human vasculature and heart correlates with low-grade inflammation and causes eNOS-NO/ROS imbalance","authors":"Ali Mroueh, Paola Algara-Suarez, Walaa Fakih, Dal-Seong Gong, Kensuke Matsushita, Sin-Hee Park, Said Amissi, Cyril Auger, Gilles Kauffenstein, Nicolas Meyer, Patrick Ohlmann, Laurence Jesel, Michael Paul Pieper, Benjamin Marchandot, Olivier Morel, Jean-Philippe Mazzucotelli, Valérie B Schini-Kerth","doi":"10.1093/cvr/cvae257","DOIUrl":"https://doi.org/10.1093/cvr/cvae257","url":null,"abstract":"Aims Sodium-glucose co-transporter 2 inhibitors (SGLT2i) show a cardioprotective effect in heart failure and myocardial infarction, pathologies often associated with low-grade inflammation. This cross-sectional study aims to investigate whether low-grade inflammation regulates SGLT2 expression and function in human vasculature, heart, and endothelial cells (ECs). Methods and results Human internal thoracic artery (ITA), left ventricle (LV) specimens, and cultured porcine coronary artery ECs were used. Expression of target molecules was assessed using RT-qPCR, western blot analysis, and immunofluorescence staining, and the generation of reactive oxygen species (ROS) and nitric oxide (NO) using fluorescent probes. The function of SGLT2 was investigated using empagliflozin and SGLT1 or 2 siRNA. SGLT2 mRNA and protein levels in ITA and LV specimens were correlated with the level of low-grade inflammation, markers of the angiotensin system, and EC activation. SGLT2 staining was observed in the ITA endothelium and smooth muscle, the coronary microcirculation, and cardiomyocytes. Elevated ROS formation in high SGLT2-expressing specimens was reduced by inhibition of the angiotensin system, SGLT2, and TNF-α. Exposure of ECs to IL-1ß, IL-6, and TNF-α led to an increase in SGLT1 and SGLT2 mRNA and protein expression, up-regulation of components of the angiotensin system, enhanced ROS and decreased NO formation, and activation of NF-κB. The stimulatory effect of TNF-α was prevented by N-acetylcysteine and inhibition of the angiotensin system, SGLT2 but not SGLT1, and NF-κB. Conclusion Low-grade inflammation is closely associated with SGLT2 expression in human vasculature and heart, and this response contributes to a feedforward mechanism with the AT1R/NADPH oxidase pathway to cause eNOS-NO/ROS imbalance.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"38 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908294","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":"Interleukin 11 therapy causes acute left ventricular dysfunction.","authors":"Mark Sweeney, Katie O'Fee, Chelsie Villanueva-Hayes, Ekhlas Rahman, Michael Lee, Chung Nga Tam, Eneko Pascual-Navarro, Henrike Maatz, Eric L Lindberg, Konstantinos Vanezis, Chrishan J Ramachandra, Ivan Andrew, Emma R Jennings, Wei-Wen Lim, Anissa A Widjaja, David Carling, Derek J Hausenloy, Norbert Hübner, Paul J R Barton, Stuart A Cook","doi":"10.1093/cvr/cvae224","DOIUrl":"10.1093/cvr/cvae224","url":null,"abstract":"<p><strong>Aims: </strong>Interleukin 11 (IL11) was initially thought important for platelet production, which led to recombinant IL11 being developed as a drug to treat thrombocytopenia. IL11 was later found to be redundant for haematopoiesis, and its use in patients is associated with unexplained and severe cardiac side effects. Here, we aim to identify, for the first time, direct cardiomyocyte toxicities associated with IL11, which was previously believed cardioprotective.</p><p><strong>Methods and results: </strong>We injected recombinant mouse lL11 (rmIL11) into mice and studied its molecular effects in the heart using immunoblotting, qRT-PCR, bulk RNA-seq, single nuclei RNA-seq (snRNA-seq), and assay for transposase-accessible chromatin with sequencing (ATAC-seq). The physiological impact of IL11 was assessed by echocardiography in vivo and using cardiomyocyte contractility assays in vitro. To determine the activity of IL11 specifically in cardiomyocytes, we made two cardiomyocyte-specific Il11ra1 knockout (CMKO) mouse models using either AAV9-mediated and Tnnt2-restricted (vCMKO) or Myh6 (m6CMKO) Cre expression and an Il11ra1 floxed mouse strain. In pharmacologic studies, we studied the effects of JAK/STAT inhibition on rmIL11-induced cardiac toxicities. Injection of rmIL11 caused acute and dose-dependent impairment of left ventricular ejection fraction (saline: 62.4% ± 1.9; rmIL11: 32.6% ± 2.9, P < 0.001, n = 5). Following rmIL11 injection, myocardial STAT3 and JNK phosphorylation were increased and bulk RNA-seq revealed up-regulation of pro-inflammatory pathways (TNFα, NFκB, and JAK/STAT) and perturbed calcium handling. snRNA-seq showed rmIL11-induced expression of stress factors (Ankrd1, Ankrd23, Xirp2), activator protein-1 (AP-1) transcription factor genes, and Nppb in the cardiomyocyte compartment. Following rmIL11 injection, ATAC-seq identified the Ankrd1 and Nppb genes and loci enriched for stress-responsive, AP-1 transcription factor binding sites. Cardiomyocyte-specific effects were examined in vCMKO and m6CMKO mice, which were both protected from rmIL11-induced left ventricular impairment and molecular pathobiologies. In mechanistic studies, inhibition of JAK/STAT signalling with either ruxolitinib or tofacitinib prevented rmIL11-induced cardiac dysfunction.</p><p><strong>Conclusions: </strong>Injection of IL11 directly activates IL11RA/JAK/STAT3 in cardiomyocytes to cause acute heart failure. Our data overturn the earlier assumption that IL11 is cardioprotective and explain the serious cardiac side effects associated with IL11 therapy.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"2220-2235"},"PeriodicalIF":10.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388299","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":"When cell mechanics meets epitranscriptomics: reduction of m6A in Piezo2 RNA ameliorates cardiac fibrosis.","authors":"Gloria Garoffolo, Maurizio Pesce","doi":"10.1093/cvr/cvae247","DOIUrl":"10.1093/cvr/cvae247","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"2158-2159"},"PeriodicalIF":10.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799315","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: Modulation of lncRNA links endothelial glycocalyx to vascular dysfunction of tyrosine kinase inhibitor.","authors":"","doi":"10.1093/cvr/cvae233","DOIUrl":"10.1093/cvr/cvae233","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"2321"},"PeriodicalIF":10.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589605","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":"GDF15 antagonism limits severe heart failure and prevents cardiac cachexia.","authors":"Minoru Takaoka, John A Tadross, Ali B A K Al-Hadithi, Xiaohui Zhao, Rocío Villena-Gutiérrez, Jasper Tromp, Shazia Absar, Marcus Au, James Harrison, Anthony P Coll, Stefan J Marciniak, Debra Rimmington, Eduardo Oliver, Borja Ibáñez, Adriaan A Voors, Stephen O'Rahilly, Ziad Mallat, Jane C Goodall","doi":"10.1093/cvr/cvae214","DOIUrl":"10.1093/cvr/cvae214","url":null,"abstract":"<p><strong>Aims: </strong>Heart failure and associated cachexia is an unresolved and important problem. This study aimed to determine the factors that contribute to cardiac cachexia in a new model of heart failure in mice that lack the integrated stress response (ISR) induced eIF2α phosphatase, PPP1R15A.</p><p><strong>Methods and results: </strong>Mice were irradiated and reconstituted with bone marrow cells. Mice lacking functional PPP1R15A, exhibited dilated cardiomyopathy and severe weight loss following irradiation, whilst wild-type mice were unaffected. This was associated with increased expression of Gdf15 in the heart and increased levels of GDF15 in circulation. We provide evidence that the blockade of GDF15 activity prevents cachexia and slows the progression of heart failure. We also show the relevance of GDF15 to lean mass and protein intake in patients with heart failure.</p><p><strong>Conclusion: </strong>Our data suggest that cardiac stress mediates a GDF15-dependent pathway that drives weight loss and worsens cardiac function. Blockade of GDF15 could constitute a novel therapeutic option to limit cardiac cachexia and improve clinical outcomes in patients with severe systolic heart failure.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"2249-2260"},"PeriodicalIF":10.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307167","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":"Inflammation and heart failure: are we facing a 'hedgehog's dilemma'?","authors":"Stefano Ministrini, Giovanni G Camici","doi":"10.1093/cvr/cvae246","DOIUrl":"10.1093/cvr/cvae246","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"2155-2157"},"PeriodicalIF":10.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643714","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}