Cardiovascular Research最新文献

{"title":"Sphingosine-1-phosphate is a potent vasoactive regulator of human coronary arteries via endothelial S1PR1-mediated NO release.","authors":"Éva Ruisanchez, Anna Janovicz, Aliz Majer, Nóra M Kerkovits, Krisztina E Vén, Imre Babay, Olivér Dinnyés, Balázs Besztercei, Bernadett Balázs, Givi Damenija, Zsuzsanna Miklós, Tamás Radovits, Béla Merkely, Bodo Levkau, Gábor J Tigyi, Zoltán Benyó","doi":"10.1093/cvr/cvag227","DOIUrl":"https://doi.org/10.1093/cvr/cvag227","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147399","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":"Differential cardiac remodelling: patterns of cardiomyocyte morphometry in multiple patient conditions.","authors":"Sandeep Manandhar, Yuxin Wu, Tilak Pathak, Kenneth B Margulies, Anant Madabhushi, Eliot G Peyster","doi":"10.1093/cvr/cvag166","DOIUrl":"10.1093/cvr/cvag166","url":null,"abstract":"<p><strong>Aims: </strong>Cardiac remodelling drives heart failure (HF), yet microstructural drivers in human tissue remain poorly defined due to the limited resolution of clinical imaging. This study sought to quantitatively assess cardiomyocyte morphometry and its relationship with clinical phenotypes.</p><p><strong>Methods and results: </strong>We developed MyoSAM, a deep learning framework for quantitative morphometric characterization of H&E-stained whole-slide images (N = 334 patients). Cardiomyocyte size was quantified using the myocyte maximum inscribed circle (MMIC) radius, along with measures of nuclear size and perinuclear-halo size, interstitial and macrodomain stromal fractions. Independent associations between these histological features and clinical variables were assessed using multivariable regression and patient-level linear mixed-effects models to account for clustering of cellular measurements within individuals. MMIC radius was the strongest histological predictor of left ventricular mass index (LVMI; P < 0.001) and was positively correlated with clinical HF (Pearson's r = 0.77, P < 0.001). In severe coronary artery disease, the association between LVMI and MMIC radius was significantly attenuated (P = 0.001), indicating that myocyte hypertrophy was diminished despite increased mass; instead, remodelling shifted towards greater interstitial stromal expansion (P = 0.025). Males exhibited larger MMIC radii than females (fold-changes 1.08, P = 0.003). Distinct aetiology-specific signatures emerged: anthracycline-treated hearts showed large MMIC radii and perinuclear halos with minimal stroma, while non-ischaemic cardiomyopathy exhibited the greatest nuclear enlargement and stromal macrodomain expansion.</p><p><strong>Conclusion: </strong>Computational pathology enables high-resolution characterization of myocardial remodelling, revealing distinct microstructural phenotypes across sex, coronary disease burden, and HF aetiology that may improve cardiac phenotyping and risk stratification.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1964-1977"},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618492","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":"Assessing cardiomyocyte hypertrophy? Let's circle back on that!","authors":"Ilse S Altenburg, Diederik W D Kuster","doi":"10.1093/cvr/cvag195","DOIUrl":"10.1093/cvr/cvag195","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1888-1890"},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890827","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":"Cytokine-associated ROS and Ca2+ dysregulation in severe inflammatory cardiomyopathy.","authors":"Phillip Suwalski, Ainoosh Golpour, January Weiner, Nicolas Musigk, Felix Balzer, Niklas Giesa, Ali Amr, Joanna Zyla, Peter Ganz, Hafiza Nosheen Saleem, Johannes Trebing, Farbod Sedaghat-Hamedani, Benjamin Meder, Stefan M Gold, Antje Ebert, Dieter Beule, Ulf Landmesser, Bettina Heidecker","doi":"10.1093/cvr/cvag099","DOIUrl":"10.1093/cvr/cvag099","url":null,"abstract":"<p><strong>Aims: </strong>Inflammatory cardiomyopathy (iCMP) is a leading cause of heart failure, with limited therapeutic options. Excessive cytokine levels are implicated in adverse outcomes, but their pathomechanism in iCMP is poorly understood. We sought to identify key cytokines involved in severe iCMP and elucidate their potential contribution to cardiomyocyte injury.</p><p><strong>Methods and results: </strong>Cytokines were analysed in patients with severe biopsy-proven iCMP (n = 63; LVEF ≤ 35%) and validated in a national cohort (n = 425). In vitro experiments examined the effect of the top cytokines observed in severe iCMP with regards to production of reactive oxygen species (ROS) and calcium homeostasis in induced human pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and human aortic endothelial cells (HAECs). Three proteins (COLEC-12, CRIM-1, IL-6) were associated with severe iCMP. In iPSC-CMs, these proteins increased ROS (H2DCFDA assay) and intracellular Ca2+ levels (Fluo-4AM assay), indicating cellular stress. Effects were less pronounced in HAEC. Finally, real-world data from electronic medical records suggested a possible cardioprotective effect of clinically available inhibitors targeting these cytokines, although these findings remain exploratory and require confirmation in controlled studies.</p><p><strong>Conclusion: </strong>COLEC-12, CRIM-1, and IL-6 are elevated in severe iCMP and induce oxidative stress and calcium dysregulation in cultured cardiomyocytes. These findings highlight their potential as possible future therapeutic targets.</p><p><strong>Clinical trial number: </strong>ClinicalTrials.gov Identifier: NCT04265040, NCT02187263.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1978-1991"},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857014","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":"Integrated management of atrial fibrillation with digital health support: a pooled analysis of individual participant data from the mAFA-II and MIRACLE-AF trials.","authors":"Gregory Y H Lip, Yang Chen, Mingfang Li, Yutao Guo, Minglong Chen","doi":"10.1093/cvr/cvag173","DOIUrl":"10.1093/cvr/cvag173","url":null,"abstract":"<p><strong>Aims: </strong>Adherence with a holistic or integrated care management of atrial fibrillation (AF) based on the AF better care (ABC) pathway has been associated with improved clinical outcomes. Two prospective randomized trials (mAFA and MIRACLE-AF) have evaluated this approach. The multicentre mAFA-II trial delivered the ABC pathway via mobile health using an mAFA App, while the MIRACLE-AF trial relied on village doctors supported by telehealth in rural communities. We conducted a pooled analysis of individual participant data to assess the overall efficacy of ABC pathway-based management in patients with AF.</p><p><strong>Methods and results: </strong>We combined patient-level data from the mAFA-II and MIRACLE-AF trials. The primary endpoint was defined as a composite of all-cause mortality, ischaemic stroke, haemorrhagic stroke, heart failure (HF), acute coronary syndrome (ACS), and major bleeding events. The secondary endpoints included individual components and two grouped outcomes: all stroke and HF/ACS. A one-stage marginal Cox proportional hazards model stratified by trial and with robust standard errors clustered at the site level was used, with adjustment for CHA2DS2-VASc and other clinically relevant baseline variables. Cumulative event rates were estimated using Kaplan-Meier methods. Subgroup and sensitivity analyses were conducted to assess the robustness of the findings. Between-trial heterogeneity was further explored using a two-stage approach, incorporating trial-level effect estimates and inverse-variance weighting. We studied 4363 patients with AF [mean age 70.3 (SD 12.8) years; 60.5% male]. During 0.8 [SD 0.4] years of follow-up, the primary endpoint occurred in 329 (7.5%). Kaplan-Meier curves demonstrated lower cumulative incidence of events in the intervention group. On multivariable mixed-effects Cox models, the intervention group demonstrated a significantly lower risk of the primary endpoint compared to the control group (adjusted hazard ratio: 0.72; 95% confidence interval: 0.56-0.93). Subgroup analyses suggested potential effect modification, whereas sensitivity analyses consistently supported the primary findings. A two-stage analysis showed directionally consistent effects across trials for the primary endpoint.</p><p><strong>Conclusion: </strong>In this pooled individual participant data from two prospective randomized trials, ABC pathway-based integrated care was associated with improved clinical outcomes in patients with AF vs. usual care, with the observed benefit primarily driven by reductions in HF/ACS-related events rather than classical AF-specific outcomes, supporting further implementation studies and context-specific adoption in clinical practice.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1936-1946"},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860302","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":"Multi-omic profiling of cardiomyocyte ageing and functional decline.","authors":"Dogacan Yucel, Michael A Trembley, Qingen Ke, Zexuan Wu, Durgesh Bonde, Peter M Kang, William T Pu","doi":"10.1093/cvr/cvag165","DOIUrl":"10.1093/cvr/cvag165","url":null,"abstract":"<p><strong>Aims: </strong>Ageing is the strongest risk factor for heart failure, yet the molecular mechanisms underlying cardiomyocyte (CM) ageing remain unclear. We aimed to map the transcriptomic and epigenomic landscape of CM ageing and to test whether DNA hypermethylation is a causal driver of diastolic dysfunction.</p><p><strong>Methods and results: </strong>We performed single-nucleus multi-omics (concurrent snRNA-seq and snATAC-seq) on 4- and 28-month-old ventricular myocardium of C57BL/6J mice. Aged CMs showed widespread chromatin remodelling, with 28 324 regions having greater accessibility compared to only two with reduced accessibility. 1963 genes were differentially expressed in aged ventricular CMs, with 78.5% neighbouring differentially accessible regions. Promoter accessibility positively associated with expression. Reduced-representation bisulphite sequencing of ventricular CM nuclei identified 1422 regions associated with genes that were hypermethylated in aged CMs, compared to only 167 that were hypomethylated. CpG hypermethylation inversely correlated with differential gene expression. Multi-omic integration revealed ageing signatures shared across cell types and identified the long non-coding RNA Gm12381 as a CM-selective ageing marker. To test whether DNA hypermethylation is associated with ageing phenotypes, we used an engineered cardiotropic AAV (MyoAAV) to overexpress Dnmt3a in adult hearts. Dnmt3a overexpression induced CM hypermethylation, causing cardiac hypertrophy and diastolic dysfunction, key ageing phenotypes, and altering the transcriptome profile towards that of aged CMs.</p><p><strong>Conclusion: </strong>Gain of chromatin accessibility and CpG hypermethylation associated with transcriptomic reprogramming characterize CM ageing. Experimental elevation of DNA methylation is sufficient to induce diastolic dysfunction and hypertrophy, supporting DNMT3A-mediated hypermethylation as a mechanistic driver. Further work should test whether attenuating methylation prevents or reverses age-related cardiac dysfunction.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"2009-2023"},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629234","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":"CardioGene: a comprehensive and integrative post-GWAS resource for exploring the genetic basis of cardiovascular diseases.","authors":"Kaiyang Chen, Mengting Shao, Xiang Guan, Changhui Zhu, Haoran Chen, Yumin Zhu, Chen Cao, Jingyi Sheng, Ning Gu","doi":"10.1093/cvr/cvag179","DOIUrl":"10.1093/cvr/cvag179","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1897-1900"},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812046","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":"Could defining arterial resilience identify protective factors for vascular ageing?","authors":"Marina Cecelja, Phil Chowienczyk, Claire J Steves","doi":"10.1093/cvr/cvag196","DOIUrl":"10.1093/cvr/cvag196","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1881-1884"},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015591","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":"Renin-angiotensin system inhibition, erythropoiesis, and aerobic training responsiveness.","authors":"Tórur Sjúrðarson, Magni Mohr, Nikolai B Nordsborg","doi":"10.1093/cvr/cvag228","DOIUrl":"https://doi.org/10.1093/cvr/cvag228","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147610","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":"Muting lateralized Cx43 hemichannels to rescue the stressed Duchenne heart.","authors":"Mehdi Badaoui, Marc Chanson, Brenda R Kwak","doi":"10.1093/cvr/cvag194","DOIUrl":"10.1093/cvr/cvag194","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1885-1887"},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890765","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}