Cardiovascular Research最新文献

{"title":"Decor(at)i(o)n-less is more?","authors":"Felix A Trogisch, Joerg Heineke","doi":"10.1093/cvr/cvaf178","DOIUrl":"https://doi.org/10.1093/cvr/cvaf178","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205777","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":"RRAD-reduction reveals efficacy of targeting L-type calcium channel regulation for treatment of heart failure","authors":"Garrett Elmore, Sarisha S Lohano, Nicholas M McVay, Bryana M Levitan, Andrea Sebastian, Kyle W Barker, Alec Dupont, Steven W Leung, Riham R E Abouleisa, Pretty R Mathew, Austin Wellette-Hunsucker, Austin T Minton, Kenneth S Campbell, Solomon W Harrar, Mohammad Mehri, Jonathan F Wenk, Tamer M A Mohamed, Douglas A Andres, Jonathan Satin","doi":"10.1093/cvr/cvaf169","DOIUrl":"https://doi.org/10.1093/cvr/cvaf169","url":null,"abstract":"Aims Heart failure with reduced ejection fraction (HFrEF) is a major health problem. Increasing L-type calcium channel (LTCC) activity deteriorates heart function; however, myocardial RRAD knockout (cRADΔ/Δ) instills tonic modulated LTCC current (ICa,L) that preserves healthy myocardium. Thus, we chose to challenge the dogma that enhanced trigger Ca2+ is maladaptive. The study objective was to test the hypothesis that modulated ICa,L in cRADΔ/Δ mice rescues dilated cardiomyopathy by providing tonic modulated trigger Ca2+. Methods and Results Mouse and human models were tested. The muscle lim protein knockout mouse (MLPKO) is a murine model of dilated cardiomyopathy (DCM) and HFrEF. The experimental timeline was to induce cRADΔ/Δ after onset of DCM (2.5 months of age) and follow subjects for up to 1-year. Longitudinal echocardiography and cardiac magnetic resonance imaging (CMR) showed that cRADΔ/Δ intervention rescued systolic function. Patch clamp recordings of isolated cardiomyocytes of MLPKO with cRADΔ/Δ demonstrated augmented LTCC activity, along with rescue of dysfunctional Ca2+ handling and sarcomere function. Bulk RNAseq of hearts demonstrated downregulated pathological signaling cascades and pro-hypertrophic gene expression which comported with the reduction in eccentric hypertrophy observed with gravimetrics, CMR, and echocardiography. RRAD knockdown effects translate from mouse to human heart. Ventricle slices from HFrEF patients were treated with lentiviral shRNA targeting RRAD and recapitulated the inotropic and lusitropic effects observed in the mouse model of DCM. Conclusions Induction of cardiomyocyte-restricted RAD knockout in MLPKO mice after onset of DCM rescued cardiac dysfunction and attenuated pathological remodeling. cRADΔ/Δ intervention provided positive inotropy and lusitropy and reverted transcriptional signatures towards healthy myocardium. This study introduces targeting myocardial RAD regulation of the LTCC as a novel therapeutic strategy for systolic heart failure.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"9 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203249","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":"ESC Congress: celebrating cardiovascular innovation, global collaborations, and patient-centered care.","authors":"Tomasz J Guzik, Thomas F Lüscher","doi":"10.1093/cvr/cvaf141","DOIUrl":"10.1093/cvr/cvaf141","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1635-1637"},"PeriodicalIF":13.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944115","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":"The new generation of small interfering RNAs directed against apoprotein(a): focus on the safety and efficacy of zerlasiran and lepodisiran.","authors":"Andrea Baragetti,Giuseppe Danilo Norata","doi":"10.1093/cvr/cvaf153","DOIUrl":"https://doi.org/10.1093/cvr/cvaf153","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"106 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182638","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":"Loss of primary cilia triggers leaflet remodelling and bicuspid aortic valve formation.","authors":"Damien Marchese, Stéphane Zaffran","doi":"10.1093/cvr/cvaf150","DOIUrl":"10.1093/cvr/cvaf150","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1645-1646"},"PeriodicalIF":13.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944131","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":"Unravelling the hidden complexity of titin splicing variants.","authors":"Diane Fatkin, Renee Johnson","doi":"10.1093/cvr/cvaf151","DOIUrl":"10.1093/cvr/cvaf151","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1640-1641"},"PeriodicalIF":13.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944121","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":"Platelet-leukocyte aggregates in cardiovascular disease: prognostic significance and therapeutic potential.","authors":"Jiaying Han, Conor J Bloxham, Kilian Kirmes, Giacomo Viggiani, Leonhard P Unkelbach, Moritz von Scheidt, Stephanie G Kühne, Isabell Bernlochner, Gianluigi Condorelli, Philip W J Raake, Dario Bongiovanni","doi":"10.1093/cvr/cvaf105","DOIUrl":"10.1093/cvr/cvaf105","url":null,"abstract":"<p><p>Initially recognized for their role in vascular haemostasis, platelets are now understood to be critical regulators of inflammation and immune responses through complex interactions with immune cells. Key to this role is the formation of platelet-leukocyte aggregates (PLAs), with platelet-monocyte aggregates (PMAs) representing the most thoroughly studied type in cardiovascular disease. PLAs form through the binding of platelet surface P-selectin to P-selectin glycoprotein ligand on leukocytes, an early interaction that may trigger broader inflammatory cascades. Recent studies link circulating PMAs with in vivo platelet activation and elevated PMA levels in patients with high thrombogenic risk, such as those with diabetes and acute myocardial infarction. Furthermore, PMA levels correlate with disease severity and long-term cardiovascular outcomes, highlighting their potential as prognostic biomarkers for adverse cardiovascular events. Therapeutic strategies, such as antiplatelet agents and P-selectin antagonists, have demonstrated efficacy in the inhibition of PLA formation. However, the development of selective inhibitors that preserve the haemostatic and immune functions of platelets remains an unmet clinical need. Despite significant progress, the precise biological functions and underlying mechanisms of PLAs are not fully understood. This review integrates preclinical and clinical data to provide a comprehensive overview of platelet-leukocyte biology, with a focus on the prognostic role and therapeutic potential of PLAs in cardiovascular disease.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1679-1696"},"PeriodicalIF":13.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246641","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":"Precision medicine requires precision proteomics: Discordance between proteomic and clinical assays in UK Biobank.","authors":"Bhawana Singh,Ioanna Tzoulaki,Manuel Mayr","doi":"10.1093/cvr/cvaf167","DOIUrl":"https://doi.org/10.1093/cvr/cvaf167","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"64 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140279","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":"Iron regulatory proteins secure iron availability in skeletal muscle to preserve exercise tolerance in heart failure.","authors":"Bomee Chung,Wenke Jonas,Fatemeh Rostami,Zulaikha Malik,Malgorzata Szaroszyk,Magdolna Levay,James Thackeray,Mario Ost,Steven Nowak,Jan Hegermann,Thomas Wieland,Andreas Pich,Frank M Bengel,Johann Bauersachs,Kai C Wollert,Joerg Heineke,Annette Schürmann,Tibor Kempf","doi":"10.1093/cvr/cvaf173","DOIUrl":"https://doi.org/10.1093/cvr/cvaf173","url":null,"abstract":"AIMSIron deficiency (ID) is a frequent comorbidity in heart failure (HF) and contributes to exercise intolerance. Tissue iron levels are maintained by cellular iron uptake, sequestration, and release, processes that are tightly controlled by iron regulatory proteins (IRP). Our aim was to explore the role of IRP activity in skeletal muscle function and exercise capacity during HF.METHODS AND RESULTSWe observed that skeletal muscle ID is associated with IRP1 and 2 inactivation 12 weeks after transverse aortic constriction (TAC) in mice with left ventricular (LV) dysfunction and cachexia. To understand the functional implications of IRP inactivation in skeletal muscle, we generated skeletal muscle-specific Irp1/2 knock-out mice (SkM-Irp1/2-KO). These mice developed muscle ID, along with lower transferrin receptor 1 (TFR1) levels and decreased non-haem iron content, within 5 weeks after birth. SkM-Irp1/2-KO mice exhibited shorter running distances and slower velocities during treadmill exercise. Transcriptomic analysis revealed upregulation of gene clusters associated with endoplasmic reticulum stress, atrophy, mitochondrial dysfunction, and inflammation. Moreover, enhanced glycolysis, increased 18F-deoxyglucose uptake in quadriceps, and faster plasma glucose clearance were detected in SkM-Irp1/2-KO versus control mice. In contrast, SkM-Irp1/2-KO mice had markedly reduced complex I and II expression, a change that confirmed defects in oxidative phosphorylation.CONCLUSIONSHF leads to IRP1/2 inactivation, ID, and metabolic dysfunction in skeletal muscle in mice. IRP1/2 inactivation in skeletal muscle causes ID, impairs oxidative energy production, and promotes exercise intolerance by reducing the capacity for effective energy utilisation.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"41 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134072","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":"Beyond triglycerides lowering: rethinking the role of eicosapentaenoic acid in lipoprotein biology.","authors":"Amedeo Tirandi,Anina Künzli,Giovanni G Camici","doi":"10.1093/cvr/cvaf175","DOIUrl":"https://doi.org/10.1093/cvr/cvaf175","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"13 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134073","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}