Cardiovascular Research最新文献

{"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}

{"title":"Unequal survival after ischaemic heart disease in Eastern Europe: a sex-specific GBD 2023 analysis.","authors":"Raffaele Bugiardini, Veaceslav Sirbu, Olivia Manfrini, Lina Badimon, Edina Cenko, Davor Milicic, Nick Townsend, Martha Gulati, Tania Rahaman, Andrejs Erglis, Olivija Dobiliene, Chris P Gale","doi":"10.1093/cvr/cvag222","DOIUrl":"https://doi.org/10.1093/cvr/cvag222","url":null,"abstract":"<p><strong>Aims: </strong>Sex disparities in ischaemic heart disease (IHD) outcomes are well documented in Western Europe, but remain poorly characterized across Eastern Europe, a region marked by substantial mortality inequalities. We aimed to determine whether population-level case fatality among individuals living with IHD differed by sex in Eastern Europe and to identify modifiable risk factors associated with disparities.</p><p><strong>Methods and results: </strong>We analysed sex-specific estimates from the Global Burden of Disease 2023 study for seven Eastern European countries. Age-standardized IHD mortality and prevalence rates were combined to derive mortality-to-prevalence ratios (MPRs) as a measure of population-level case fatality. Risk factor-attributable mortality was similarly normalized to prevalence. Estonia, which had the lowest MPRs (men 3.00%; women 1.77%), served as the benchmark for Z-score analyses (|Z| ≥ 1.96 = P < 0.05). In 2011, women in 5 of 6 countries had higher MPRs than Estonian women (Z = 2.25-4.35), whereas men showed excess MPRs in only 3 countries (Z = 2.29-3.18). By 2023, all 6 countries showed higher female MPRs than Estonia (Z = 3.27-5.14). In men, excess MPRs persisted in Latvia, the Russian Federation and Ukraine (Z = 2.48-3.16) and emerged in Belarus (Z = 4.79) but remained non-significant in Lithuania and the Republic of Moldova.Female-specific benchmark signals were observed for high fasting plasma glucose in Belarus and the Republic of Moldova, and for high systolic blood pressure in Lithuania, the Republic of Moldova, and the Russian Federation.</p><p><strong>Conclusions: </strong>Pronounced sex disparities in IHD population-level case fatality persist across Eastern Europe. Lithuania and the Republic of Moldova showed the most consistent female disadvantage. Excess female population-level case fatality was most consistently associated with key modifiable risk factors.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135209","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 novel strategy to protect ischaemic heart: driving FLT1 transcriptional switch.","authors":"Giulia Bianchi, Giuseppe Lembo","doi":"10.1093/cvr/cvag220","DOIUrl":"https://doi.org/10.1093/cvr/cvag220","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126673","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":"Growth hormone and aging cardiomyocytes","authors":"Eckhard U Alt,Reza Izadpanah","doi":"10.1093/cvr/cvag225","DOIUrl":"https://doi.org/10.1093/cvr/cvag225","url":null,"abstract":"Abstract The age-related decline in growth hormone (GH) secretion, termed the somatopause, parallels the structural and functional deterioration of the aging heart. How this endocrine withdrawal translates into myocardial failure at the molecular level remains incompletely mapped. GH/insulin-like growth factor 1 (IGF-1) signaling acts via PI3K/Akt/mTOR and Ras/MAPK/c-Myc cascades on four processes central to cardiac aging: Akt-dependent nuclear retention of telomerase reverse transcriptase (TERT), established primarily in non-cardiomyocyte models; PGC-1α-driven mitochondrial biogenesis; suppression of the p53/p16INK4a senescence program; and metabolic-epigenetic regulation of cell-cycle competence via α-ketoglutarate/KDM5 and JMJD3 chromatin gating. In mouse cardiomyocytes, positive transcription elongation factor b (P-TEFb) is rate-limiting for Myc-driven proliferation, plausibly explaining why adult cardiomyocytes retain latent cell-cycle machinery yet rarely divide. A candidate GHRHR-HIF-1α axis, presently supported by preprint evidence, is examined as an emerging hypothesis for cell-type-selective cardioprotection independent of systemic GH. We integrate these strands along a single tractable axis: IGF-1/Akt/TERT/p53/PGC-1α with metabolic-epigenetic modulation. The 2025 Marra trial (NCT03775993; 64 randomized, 45 completers; surrogate and functional endpoints not powered for clinical events) reports that physiological GH restoration improves peak VO2 (+3.1 vs −1.8 mL/kg/min, P&amp;lt;0.01), NYHA class, and quality of life in heart failure with confirmed GH deficiency. A meta-analysis of 25 studies quantifies the U-shaped IGF-1-heart failure relationship, with the HF-versus-control IGF-1 difference derived from six of those studies. Plasma proteomic organ-aging signatures show accelerated cardiac aging is associated with 2.5-fold heart-failure risk. We present a hypothesis-generating framework identifying GH/IGF-1 axis restoration as a candidate determinant of heart-failure progression, warranting event-driven confirmation.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"166 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087903","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":"Improved plaque composition from intensive medical treatment in women with angina and non-obstructive coronary disease","authors":"Joel Lenell,Guadalupe Flores Tomasino,Donghee Han,Rafal Wolny,Caroline Park,Kajetan Grodecki,Jacek Kwiecinski,Emily Xing,Nipun Manral,Folahanmi Asebiomo,Divyani Goyal,Vinicius F Calsavara,Osama Dasa,Daniel S Berman,Piotr J Slomka,Matthew Budoff,Eileen Handberg,Colin Berry,Carl J Pepine,Janet Wei,Leslee Shaw,Martha Gulati,Noel Bairey Merz,Balaji Tamarappoo,Damini Dey","doi":"10.1093/cvr/cvag174","DOIUrl":"https://doi.org/10.1093/cvr/cvag174","url":null,"abstract":"Abstract Aims Among women with suspected ischaemia and non-obstructive coronary artery disease (INOCA), the temporal effect of combination intensive medical treatment (IMT) with angiotensin-converting enzyme inhibitors or receptor blockers, statins, and aspirin on coronary plaque composition is not known. This prospective ancillary study examined changes in atherosclerotic plaque volumes and composition (percentage of total plaque volume) over time between IMT and usual care (UC). Methods and results Participants from the randomized WARRIOR trial with the presence of plaque on their first coronary computed tomography angiography (CCTA) were enrolled for a follow-up CCTA at least 2 years after randomization. Volumes and volumetric composition (percentage of total plaque volume) of non-calcified plaque (NCP), low-density NCP (LD-NCP, defined as NCP &amp;lt;30 HU), and calcified plaque (CP) were quantified over the coronary tree in the serial scans. Participants (n = 186) completed both scans with good image quality (94 IMT arm and 92 UC arm). Overall mean age was 61.0 years (SD ±10.9), and there were no statistically significant differences in baseline risk factors, plaque volumes, or statin treatment between the arms. There was a greater bi-annualized increase in CP volume [ΔCP volume (mm3)] in the IMT arm, 6.2 (SD ±15.5) compared to the UC arm, 3.9 (SD ±16.0), P = 0.013, and a consistent greater reduction in NCP composition [ΔNCP composition (%)] in the IMT arm, −3.9 (SD ±7.7) compared to the UC arm, −1.5 (SD ±5.8), P = 0.003, with no increase in total plaque volume. Conclusion In women with suspected INOCA, IMT reduces NCP volumetric composition to a greater extent than UC and may promote plaque stabilization.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"73 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087902","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 the vessel wall: single-cell dissection of epicardial fat–myocardial crosstalk in coronary artery disease","authors":"Nazan Puluca,Ehsan Vafadarnejad,Taiba Saleem,Charlotte Rammoser,Felix Wirth,Vanessa Schwerdt,Martina Dreßen,Irina Gottmann,Xaver Reiminger,Yilin Yan,Sabine Seeler,Keno K Bressem,Zhifen Chen,Shuangyue Li,Nico Erhard,Harald Lahm,Teodora-Cristina Georgescu,Andrea Reiter,Elda Dzilic,Ralf Günzinger,Stephanie Voss,Ulf Herold,Bernhard Voss,Keti Vitanova,Christian Braun,Valentina Leone,Maximilian Reichert,Isabel Deisenhofer,Martin Hadamitzky,Heribert Schunkert,Markus Krane,Stefanie A Doppler","doi":"10.1093/cvr/cvag189","DOIUrl":"https://doi.org/10.1093/cvr/cvag189","url":null,"abstract":"Abstract Aims Epicardial adipose tissue (EAT) has emerged as an active regulator of cardiovascular disease, yet the cellular and molecular features of myocardial-associated EAT (mEAT) in coronary artery disease (CAD) remain incompletely defined. Methods and results We performed single-nucleus RNA sequencing of mEAT from patients with CAD (n = 9), nonCAD cardiovascular surgery patients (n = 9), and forensic controls without cardiac disease (n = 2), integrated with histology, CT-based EAT volume assessment, matched right atrial myocardium analysis, and functional in vitro assays. mEAT contained diverse adipocyte, stromal, immune, and vascular cell populations. In CAD, we identified two disease-enriched inflammatory cell states, inflammatory adipogenic cells (IAC) and inflammatory stromal cells (ISC), characterized by immune activation, stress-response signalling, extracellular matrix remodelling, and impaired adipogenic features. Histological analyses confirmed enlarged adipocytes, increased fibrosis, and higher abundance of IAC/ISC-associated markers in CAD-mEAT. Exploratory integration with CT imaging suggested a possible association between increased EAT volume and enrichment of inflammatory cell states. Comparative analyses with published adipose and cardiac single-cell datasets indicated that IAC and ISC share features with previously described inflammatory adipocyte and stromal populations, while displaying a distinct marker combination enriched in CAD-associated mEAT. Cell–cell communication analyses identified THBS1–CD36 and SEMA4A/SEMA3C–NRP1/PLXNA signalling as predicted CAD-associated communication axes involving inflammatory mEAT populations and myocardial cell types. Conditioned medium from CAD-mEAT-derived adipocytes/IAC altered contractile properties of human iPSC-derived cardiomyocyte (CM) microtissues, while simultaneously impairing endothelial tube formation and migration. Recombinant THBS1 and SEMA3C partially recapitulated selected effects, whereas combined CD36 and NRP1 blockade partially attenuated endothelial and CM responses. Conclusion Together, these data provide a high-resolution map of CAD-associated mEAT remodelling and identify IAC and ISC as inflammatory cell states linked to altered adipose–vascular and adipose–myocardial signalling. These findings support the concept that cellular and molecular features of mEAT may complement imaging-based EAT assessment and inform future studies on CAD-associated adipose tissue inflammation.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"15 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087904","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":"Macrophage Smad1 drives post-infarction dysfunction by reducing angiogenesis and by promoting matrix remodeling","authors":"Bijun Chen,Shuaibo Huang,Anis Hanna,Silvia C Hernandez,Izabela Tuleta,Kevin O’Leary,Claudio Humeres,Deyou Zheng,Nikolaos G Frangogiannis","doi":"10.1093/cvr/cvag185","DOIUrl":"https://doi.org/10.1093/cvr/cvag185","url":null,"abstract":"Abstract Aims Infarct macrophages undergo dramatic phenotypic changes in response to cytokines and growth factors and serve as central effectors in cardiac repair and remodeling. Transforming Growth Factor (TGF)-β superfamily members are key regulators of macrophages and signal predominantly through activation of Smad-dependent cascades. Although the involvement of TGF-β/Smad3 in regulation of macrophage phenotype has been documented, the effects of Smad1 signaling on macrophage phenotype and function remain unknown. We aimed at examining the patterns of activation and role of macrophage Smad1 in repair and remodeling of the infarcted heart. Methods and results Macrophage Smad1 activation peaked 7 days after infarction. In vitro, TGF-β1, TGF-β3 and Bone Morphogenetic Protein (BMP)-6, potently stimulated Smad1 activation in bone marrow macrophages. To study the role of macrophage Smad1 in myocardial infarction, we generated mice with myeloid cell-specific Smad1 loss. Bioinformatic analysis of scRNA-seq data suggested broad activation of a Smad1-mediated transcriptional program in all clusters of infarct macrophages. Myeloid cell-specific Smad1 loss attenuated post-infarction adverse remodeling and ventricular dysfunction, increasing angiogenesis and decreasing extracellular matrix denaturation. Proteomic and transcriptomic analysis suggested that acquisition of an angiogenic macrophage profile in the absence of Smad1 is associated with upregulation of the angiogenic mediators CXCL12 and osteopontin and attenuated expression of the angiostatic chemokine CXCL4. However, myeloid cell–specific CXCL12 deletion in MyS1KO mice did not abolish the enhanced angiogenesis induced by Smad1 deficiency, indicating that Smad1-mediated suppression of angiogenesis likely depends on the coordinated regulation of multiple angiogenic pathways rather than on CXCL12 alone. Conclusions We demonstrate for the first time that macrophage Smad1 contributes to adverse post-infarction remodeling by regulating the balance between angiogenic and angiostatic signals and by enhancing extracellular matrix remodeling.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"37 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092264","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":"Distinct chromatin landscapes dictate resident cardiac macrophage lifecycles and functions","authors":"Anthony Wong,Shabana Vohra,Kai Ellis,Homaira Hamidzada,Brendan Cordeiro,Domien Vanneste,Rebecca Bellworthy,Christopher Arlidge,Jillian Macklin,Crystal Kantores,Abdul Momen,Sarah A Dick,Xavier Clemente-Casares,Thomas Marichal,David Langlais,Michael D Wilson,Mathieu Lupien,Slava Epelman","doi":"10.1093/cvr/cvag215","DOIUrl":"https://doi.org/10.1093/cvr/cvag215","url":null,"abstract":"Abstract Aims Three resident macrophage subsets co-exist in the homeostatic heart, exhibiting distinct origins transcriptional identities and functions. However, the underlying epigenetic architecture regulating resident cardiac macrophage subset heterogeneity is not known, which limits mechanistic understanding and therapeutic targeting. Methods and results We performed bulk and single-cell ATAC-seq to map the chromatin landscape of murine resident macrophage subsets. Integration of ATAC-seq with RNA-seq of each cardiac macrophage subset revealed two primary chromatin accessibility-based cell states that correlated with tissue residency – a CCR2- macrophage chromatin-based cell state that corresponded with resident TLF+ (TIMD4 + LYVE1 + FOLR2+) and CCR2-MHC-IIhi subsets that do not require monocytes for maintenance, and a CCR2+ chromatin-based cell state that corresponded to CCR2 + MHC-IIhi macrophages, which rely on monocyte input. Using footprint analysis, we identified subset-specific differences in transcription factor binding that explained transcriptional differences, including enriched AP-1 binding in CCR2+ macrophages and enriched MAF-family factor binding in TLF+ macrophages. Importantly, we demonstrate myeloid-specific loss of Mafb or Maf skewed macrophage subset composition toward CCR2+ macrophages and increased MHC-II expression in TLF+ macrophages. Furthermore, we identify a link between IRF8 and MHC-II, in which myeloid-specific loss of Irf8 abolished MHC-II expression exclusively in fate-mapped resident CCR2- subsets but not in CCR2+ macrophages, demonstrating a subset-specific dependency of IRF8 in modulating antigen-presentation. Conclusion Together, these data suggest tissue residency dictates chromatin accessibility and transcription factor binding in cardiac macrophages, linking epigenetic structure to monocyte-dependency, distinct gene expression patterns and critical functions such as antigen presentation.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"11 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087907","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":"Liver X receptor (LXR) signaling in macrophage inflammation and cardiometabolic disease","authors":"Lobke F Zijlstra,Menno P J de Winther,Sander Kooijman,Antonio Castrillo,Annette E Neele","doi":"10.1093/cvr/cvag214","DOIUrl":"https://doi.org/10.1093/cvr/cvag214","url":null,"abstract":"Abstract Cardiometabolic diseases profoundly remodel tissue immune landscapes, characterized by the accumulation of diverse macrophage subtypes. Among these, lipid-associated macrophages (LAMs) have emerged as an important subset that is frequently observed in cardiometabolically affected tissues. LAMs are defined by a transcriptional profile linked to lipid metabolism and processing. In parallel, the nuclear receptor liver X receptor (LXR), is a key transcription factor that regulates cholesterol efflux, fatty-acid synthesis, as well as inflammation pathways. Through these pathways, LXR agonism has been shown to limit atherosclerosis progression but also to promote hepatic steatosis. Beyond lipid metabolism, LXRs exert important immunoregulatory functions. In murine macrophages, LXR activation consistently dampens inflammatory responses. In contrast, human macrophages show more heterogeneous responses, with several studies indicating that LXRs can also promote pro-inflammatory gene programs. These species-specific differences highlight a critical gap that currently limits the translation of preclinical findings. In this review, we integrate recent insights of LXRs in LAMs and cardiometabolic disease, emphasizing species-specific differences in macrophage LXR signaling between mice and humans. We discuss the contribution of LXR isoforms and emerging mechanisms by which LXRs influence inflammatory responses, and consider their implications for therapeutic targeting.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"58 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087909","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}