Cardiovascular Research最新文献

{"title":"A novel approach to modeling 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":"https://doi.org/10.1093/cvr/cvae268","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-01-06","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":"Chemokine receptor-directed imaging, prognostication, and treatment of abdominal aortic aneurysm: can we do it all with CXCR4?","authors":"Martin Andreas, Irene M Lang","doi":"10.1093/cvr/cvae259","DOIUrl":"https://doi.org/10.1093/cvr/cvae259","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930716","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":"Taming the flame: SerpinB1 suppression of pyroptosis in pathological cardiac hypertrophy.","authors":"Beatrijs Bartelds, Daphne Merkus","doi":"10.1093/cvr/cvae262","DOIUrl":"https://doi.org/10.1093/cvr/cvae262","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920888","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":"Cardioprotection exerted by intravenous statin at index myocardial infarction event attenuates cardiac damage upon recurrent infarction","authors":"Gemma Vilahur, Soumaya Ben-Aicha, Manuel Gutiérrez, Monika Radike, Guiomar Mendieta, Lisaidy Ramos, Sebastia Alcover, Laura Casani, Gemma Arderiu, Teresa Padró, María Borrell, Lina Badimon","doi":"10.1093/cvr/cvae264","DOIUrl":"https://doi.org/10.1093/cvr/cvae264","url":null,"abstract":"Aims Recurrent acute myocardial infarction (RE-AMI) is a frequent complication after STEMI, and its association with stent thrombosis can be life-threatening. Intravenous atorvastatin (IV-atorva) administration during AMI has been shown to limit infarct size and adverse cardiac remodeling. We determined by cardiac magnetic resonance (CMR) whether the cardioprotection exerted by IV-atorva at the index AMI event translates into a better prognosis upon RE-AMI in dyslipidemic pigs. Methods and Results Hypercholesterolemic pigs underwent a first AMI (90-minute coronary balloon occlusion). During ongoing ischemia, animals received IV-atorva or vehicle. Forty days later, animals underwent RE-AMI and were sacrificed on day43. All animals remained on p.o. atorvastatin and a high-cholesterol diet from the first AMI until sacrifice. Serial CMR analysis was performed on day3 post-AMI, prior- (day40) and post-RE-AMI (day43). No differences were detected in edema formation in both animal groups during AMI and RE-AMI. Gadolinium DE-CMR revealed smaller infarcts in IV-atorva-treated animals at index event at 3days and 40days post-AMI compared to vehicle-administered pigs (p<0.05). CMR analyses post-RE-AMI revealed smaller infarcts in the animals treated with IV-atorva at index event than in the vehicle-administered pigs. These IV-atorva at index event benefits were associated with higher LVEF and normal LV wall motion in the jeopardized myocardium at RE-AMI (p<0.05 vs. vehicle). The scar region of RE-AMI of animals treated with IV-atorva at index event showed reduced cardiac inflammatory infiltrate, apoptosis and senescence activation, and increased reparative fibrosis and neovessel formation vs. vehicle-administered pigs. Animals treated with IV-atorva at index event also showed lower CRP and higher IL-10 plasma levels in the setting of RE-AMI. Conclusions The cardioprotection afforded by IV-atorva administration during an index-AMI event shows a legacy effect attenuating myocardial damage and preserving cardiac contractile function upon RE-AMI. The potential benefits of this intravenous approach should be tested in the clinical setting.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"2 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929180","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: 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}