Cardiovascular Research最新文献

{"title":"Epigenetic leash on the epitranscriptome: unveiling a novel regulatory axis in vascular smooth muscle contractility.","authors":"Jiaqi Huang,Yi Fu","doi":"10.1093/cvr/cvaf162","DOIUrl":"https://doi.org/10.1093/cvr/cvaf162","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"201 1","pages":"1803-1805"},"PeriodicalIF":10.8,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351844","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 multi-omics approach uncovers causality of IL6R on endotypes of subclinical carotid atherosclerosis and the possible role of the IL6R/OSMR pathway.","authors":"Qiao Sen Chen,Hanna M Björck,Otto Bergman,Damiano Baldassarre,Gunnar Engström,Antonio Gallo,Anders Gummesson,Ulf Hedin,Sudhir Kurl,Lars Lind,Ljubica Matic,Douw Johannes Mulder,Matteo Pirro,Kai Savonen,Stefan Söderberg,Fabrizio Veglia,Elena Tremoli,Carl Johan Östgren,Per Eriksson,Rona J Strawbridge,Bruna Gigante","doi":"10.1093/cvr/cvaf177","DOIUrl":"https://doi.org/10.1093/cvr/cvaf177","url":null,"abstract":"AIMSEndotypes integrate individual clinical and molecular data and can be used to formulate molecular subclassifications of diseases. We previously derived four endotypes of subclinical carotid atherosclerosis in a large European cohort, c-IMT and c-IMT Progression as Predictors of Vascular Events in a High-Risk European Population (IMPROVE), identifying individuals with a specific cardiovascular (CV) risk, ranging from low (endotype 1) to very high (endotype 4). Here, we investigate the mechanisms underlying the differences in CV risk observed across these four endotypes.METHODS AND RESULTSWe validated the four endotypes in SCAPIS (n = 5050) and UK Biobank (n = 50 396) using carotid plaque and carotid intima-media thickness (c-IMT) as subclinical atherosclerosis measures. Endotype 4 associated with a larger number of carotid plaques and increased c-IMT measures as compared to endotype 1. We performed a meta-analysis of individual genome wide association studies in IMPROVE (n = 3711), SCAPIS and UK Biobank, and identified 12 SNPs associated with endotypes. We investigated if they regulated gene expression and circulating protein levels. We found that rs2228145A/C at Interleukin-6 Receptor (IL6R), associated with endotype 4, regulated IL6R expression and circulating levels of OncoStatin M Receptor (OSMR), Complement Factor B (CFB) and Fibrinogen Chain A (FGA). We used rs2228145A/C as an instrument in two-sample Mendelian randomization analyses and showed that a decreasing IL6R expression, associated with increasing CFB, FGA, and OSMR circulating levels. Endotype 4, IL6R, CFB, FGA, and OSMR co-localized within 250 kb surrounding rs2228145A/C. However, only OSMR was up-regulated in advanced carotid atherosclerotic plaques in the presence of the A allele and in aortic region exposed to low wall shear stress. In the UK Biobank, we observed that each additional A allele at rs2228145 increased by 1.28-times the risk of myocardial infarction (MI) in endotype 4.CONCLUSIONRs2228145A/C associated with endotype 4 clinical and molecular characteristics and amplified the MI risk in individuals assigned to endotype 4. These effects appeared to be mediated by a crosstalk with OSMR.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"20 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339415","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":"Kinases go where the function calls.","authors":"Matilde Said,Alicia Mattiazzi,Cecilia Mundiña-Weilenmann","doi":"10.1093/cvr/cvaf197","DOIUrl":"https://doi.org/10.1093/cvr/cvaf197","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"98 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331694","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":"Allostatic-interoceptive brain network: a bridge between cardiovascular burden and dementias.","authors":"Lorenzo Carnevale","doi":"10.1093/cvr/cvaf198","DOIUrl":"https://doi.org/10.1093/cvr/cvaf198","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"24 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331695","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":"One-dimensional virtual FFR: promise, pragmatism and next steps.","authors":"Robert A Sykes,Dylan Tan,Colin Berry","doi":"10.1093/cvr/cvaf193","DOIUrl":"https://doi.org/10.1093/cvr/cvaf193","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"26 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338674","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":"Rbm20 antisense oligonucleotides alleviate diastolic dysfunction in a mouse model of cardiometabolic heart failure (HFpEF).","authors":"Mei Methawasin,Stefan Meinke,Michael H Radke,Gerrie P Farman,Zaynab Hourani,John E Smith,Wei Guo,Henk Granzier,Michael Gotthardt","doi":"10.1093/cvr/cvaf171","DOIUrl":"https://doi.org/10.1093/cvr/cvaf171","url":null,"abstract":"AIMSHeart failure with preserved ejection fraction (HFpEF) is prevalent, deadly, and difficult to treat. Risk factors such as obesity and hypertension contribute to cardiac inflammation, metabolic defects, and pathological remodelling that impair ventricular filling in diastole. Titin based stiffness is a main determinant of diastolic function and can be adjusted by the splicing regulator RNA binding motif protein 20 (RBM20). Inhibition of RBM20 using antisense oligonucleotides (ASOs) induces expression of compliant titin isoforms, which reduce stiffness. However, dose finding and documenting utility in primarily cardiometabolic disease remains challenging.METHODS AND RESULTSHere, we optimized RBM20-ASO dosing in a HFpEF mouse model that closely mimics human disease, characterized by metabolic syndrome and comorbidities, but without primary defects in titin or RBM20. Partial inhibition of RBM20 (∼50%) selectively increased compliant titin isoforms, improving diastolic function while preserving systolic performance. This intervention reduced left ventricular stiffness, enhanced relaxation, and mitigated cardiac hypertrophy, despite ongoing systemic comorbidities.CONCLUSIONOur findings demonstrate that targeting titin stiffness with Rbm20-ASOs can serve as an alternative or adjunctive therapeutic strategy for HFpEF to restore cardiac function and prevent further organ damage. The approach may offer benefits even in the presence of phenotypic heterogeneity and unresolved systemic comorbidities.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"64 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305643","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":"Insights into pulmonary remodelling in heart failure with preserved ejection fraction through transpulmonary biomarker gradients.","authors":"Misha Dagan,Anna Beale,Bing Wang,Donna Vizi,Jason E Bloom,Justin Mariani,Hitesh Patel,William Chan,Shane Nanayakkara,David M Kaye","doi":"10.1093/cvr/cvaf196","DOIUrl":"https://doi.org/10.1093/cvr/cvaf196","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"12 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305641","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":"Vitamin B6 (pyridoxal 5’ phosphate) antagonizes carotid body P2X3 receptors in hypertension","authors":"Igor S A Felippe, Thalia L Babbage, Rajaa Shaheen, Marcella Bassetto, Jui-Lin Fan, Audrys Pauza, Olivia Gold, Pratik Thakkar, Matthew Dawes, Melissa L Bates, Fiona McBryde, Samuel J Fountain, James P Fisher, Julian F R Paton","doi":"10.1093/cvr/cvaf195","DOIUrl":"https://doi.org/10.1093/cvr/cvaf195","url":null,"abstract":"Aims ATP acting on P2X3R within carotid bodies (CBs) underpins chemoreflex-mediated sympathetic overactivity in Spontaneously Hypertensive rats (SHR). Pyridoxal 5’phosphate (PLP), the active form of vitamin B6, is reported as being a non-selective P2X receptor blocker. Hence, we hypothesized that PLP antagonism of P2X3R in the CB would treat hypertension. Methods and Results Herein, we employed a multipronged approach to investigate PLP’s capability to attenuate CB hyperexcitability in hypertension. First, PLP inhibited Ca2+ responses evoked by α, β-methylene ATP in cells lines expressing human (h) P2X3R with IC50 of 8.7µM. Next, in-silico data predicted that PLP binds to the same site of Gefapixant, supporting an allosteric antagonism. Using an isolated perfused carotid artery bifurcation-CB preparation, arterial infusion of PLP (50 µM; 15 min) attenuated CBs sensory firing in SHR (P=0.012). Using the in situ working-heart brainstem preparation, carotid artery injections of PLP (1-5mM) attenuated the chemoreflex-evoked sympathetic (P=0.023) but not phrenic (P=0.62) responses; the CB was stimulated with potassium cyanide (KCN,50 µL; 0.04%). In awake telemetered SHR (n=6), intravenous infusion of PLP (48 mg/Kg/h; 30 min) attenuated KCN-evoked chemoreflex responses and reduced systolic, diastolic, and mean blood pressures (ΔMBP = -15.6 mmHg; P=0.025). Translating our results, we performed a small double-blind randomized clinical trial. In volunteers with hypertension (n=14), oral supplementation with pyridoxine hydrochloride (600 mg) attenuated the hypoxic ventilatory response only in patients with high peripheral chemoreflex sensitivity (P=0.021). Conclusion Our findings suggest that PLP binds to and antagonizes P2X3R and is a viable candidate for larger clinical trials to treat CB dysregulation in cardiovascular diseases.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"44 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295614","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":"Tirzepatide protects the heart from doxorubicin-induced cardiotoxicity by modulating endoplasmic reticulum (ER) stress and HMGCoA reductase 1 expression.","authors":"Christopher C Glembotski","doi":"10.1093/cvr/cvaf163","DOIUrl":"https://doi.org/10.1093/cvr/cvaf163","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"52 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277254","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":"Monocytes at the crossroads of aortic stenosis and myocardial damage","authors":"Nervana Issa, Alexandre Candellier, Cédric Boudot, Romain Capoulade, Hussein Ghamlouch, Magnus Bäck, Sylvain Fraineau, Youssef Bennis, Helène Eltchaninoff, Saïd Kamel, Christophe Tribouilloy, Lucie Hénaut","doi":"10.1093/cvr/cvaf186","DOIUrl":"https://doi.org/10.1093/cvr/cvaf186","url":null,"abstract":"Aortic stenosis (AS) is the most common heart valve disease in high-income countries, causing significant morbidity and mortality. It results from progressive thickening and calcification of the aortic valve (AV) leaflets, leading to AV narrowing and myocardial remodeling - both key contributors to disease progression and symptoms. With no pharmacological treatment to slow AS, aortic valve replacement (AVR) remains the only therapeutic option for symptomatic patients. However, limited understanding of AS pathophysiology and the absence of reliable prognostic markers hinder improved patient outcomes. A comprehensive reassessment of AS pathophysiology, integrating both valvular and myocardial remodeling is essential for advancing prognostic tools and therapeutic strategies. Inflammation plays a central role in these processes, drawing increasing attention to monocytes. This review provides an updated overview of monocytes’ multifaceted involvement in AS, including: i) fibrocalcific remodeling of the valve, ii) myocardial injury during disease progression, and iii) structural valve deterioration (SVD) after surgical or transcatheter AVR. We will also discuss the potential of monocyte subsets as biomarkers for AS progression and post-AVR prognosis, as well as the therapeutic targeting of monocytes to prevent AS, SVD, and subsequent myocardial dysfunction.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"71 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260625","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}