Cardiovascular Research最新文献

{"title":"Senescent CD8+ T cells: a novel risk factor in atrial fibrillation.","authors":"Xiang Li, Yangyang Bao, Ning Zhang, Changjian Lin, Yun Xie, Yue Wei, Qingzhi Luo, Jingmeng Liu, Zimo Sha, Guanhua Wu, Taojie Zhou, Qiujing Chen, Tianyou Ling, Wenqi Pan, Lin Lu, Liqun Wu, Yang Dai, Qi Jin","doi":"10.1093/cvr/cvae222","DOIUrl":"10.1093/cvr/cvae222","url":null,"abstract":"<p><strong>Aims: </strong>Immune cell alterations may play a role in the development of atrial fibrillation (AF). Our objective was to comprehensively characterize immune cells in AF, and investigate the potential mechanisms.</p><p><strong>Methods and results: </strong>Single-cell RNA sequencing and multicolour flow cytometry revealed that T cells constituted the most significant subset alterations in AF, and senescent CD8+ T cells were AF-associated subset. Senescent CD8+ T cells increased in both peripheral veins (P < 0.0001) and the left atria (P < 0.05) in patients with AF compared to non-AF control. Senescent CD8+ T cells were independently associated with AF prevalence (odds ratio = 2.876, P < 0.05) and postprocedural recurrence (hazard ratio = 22.955, P < 0.0001) using a cross-sectional study and a subsequent prospective cohort study. Senescent CD8+ T cells secreted an increased amount of interferon (IFN)-γ, which induces Ca2+ handling abnormalities in human induced pluripotent stem cell-derived atrial cardiomyocytes, and translated into an increased susceptibility to AF assessed by heart optical mapping.</p><p><strong>Conclusions: </strong>An increased amount of senescent CD8+ T cells may be a hallmark of the immune senescence phenotype in AF and potentially serve as a valid biomarker for assessing prevalence and postprocedural recurrence of AF. By connecting immune senescence with electrophysiological disturbances in AF, this research provides a potential mechanism for the involvement of senescent CD8+ T cells in proarrhythmic calcium disorders and suggests novel avenues for developing new immune-modulatory and senolytic therapies for AF.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"97-112"},"PeriodicalIF":10.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388300","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":"SerpinB1 targeting safeguards against pathological cardiac hypertrophy and remodelling by suppressing cardiomyocyte pyroptosis and inflammation initiation.","authors":"Cong Lan, Guangyao Fang, Xiuchuan Li, Xiao Chen, Yingmei Chen, Tao Hu, Xuenan Wang, Huiling Cai, Jiajin Hao, Haoran Li, Yan Zhang, Ke Peng, Zaicheng Xu, Dachun Yang, Xia Kang, Qian Xin, Yongjian Yang","doi":"10.1093/cvr/cvae241","DOIUrl":"10.1093/cvr/cvae241","url":null,"abstract":"<p><strong>Aims: </strong>While the pivotal role of inflammation in pathological cardiac hypertrophy and remodelling is widely acknowledged, the mechanisms triggering inflammation initiation remain largely obscure. This study aims to elucidate the role and mechanism of serpin family B member 1 (SerpinB1) in pro-inflammatory cardiomyocyte pyroptosis, heart inflammation, and cardiac remodelling.</p><p><strong>Methods and results: </strong>C57BL/6J wild-type, inducible cardiac-specific SerpinB1 overexpression or knockout mice underwent transverse aortic constriction (TAC) surgery. Cardiac hypertrophy and remodelling were assessed through echocardiography and histology. Cardiomyocyte pyroptosis and heart inflammation were monitored. Adeno-associated virus 9 -mediated gene manipulations and molecular assays were employed to explore the mechanisms through which SerpinB1 regulates cardiomyocyte pyroptosis and heart inflammation. Finally, recombinant mouse SerpinB1 protein (rSerpinB1) was administrated both in vivo through osmotic minipump delivery and in vitro to investigate the therapeutic potential of SerpinB1 in cardiac remodelling. Myocardial SerpinB1 overexpression was up-regulated shortly upon TAC or phenylephrine challenge, with no further elevation during prolonged hypertrophic stimuli. It is important to note that cardiac-specific overexpression of SerpinB1 markedly attenuated TAC-induced cardiac remodelling, while deletion of SerpinB1 exacerbated it. At the mechanistic level, SerpinB1 gain-of-function inhibited cardiomyocyte pyroptosis and inflammation in hypertrophic hearts; the protective effect was nullified by overexpression of either cleaved N-terminal gasdermin D or cleaved caspase-1. Co-immunoprecipitation and confocal assays confirmed that SerpinB1 directly interacts with caspase-1 in cardiomyocytes. Remarkably, rSerpinB1 replicated the cardioprotective effect against cardiac hypertrophy and remodelling.</p><p><strong>Conclusion: </strong>SerpinB1 safeguards against pathological cardiac hypertrophy and remodelling by impeding cardiomyocyte pyroptosis to suppress inflammation initiation, achieved through interaction with caspase-1 to inhibit its activation. Targeting SerpinB1 could represent a novel therapeutic strategy for treating pathological cardiac hypertrophy and remodelling.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"113-127"},"PeriodicalIF":10.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833364","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":"Slack K+ channels confer protection against myocardial ischaemia/reperfusion injury.","authors":"Anna Roslan, Katharina Paulus, Jiaqi Yang, Lucas Matt, Helmut Bischof, Natalie Längst, Sophia Schanz, Annika Luczak, Melanie Cruz Santos, Sandra Burgstaller, David Skrabak, Nadja I Bork, Roland Malli, Achim Schmidtko, Meinrad Gawaz, Viacheslav O Nikolaev, Peter Ruth, Rebekka Ehinger, Robert Lukowski","doi":"10.1093/cvr/cvae155","DOIUrl":"10.1093/cvr/cvae155","url":null,"abstract":"<p><strong>Aims: </strong>Na+-activated Slack potassium (K+) channels are increasingly recognized as regulators of neuronal activity, yet little is known about their role in the cardiovascular system. Slack activity increases when intracellular Na+ concentration ([Na+]i) reaches pathophysiological levels. Elevated [Na+]i is a major determinant of the ischaemia and reperfusion (I/R)-induced myocardial injury; thus, we hypothesized that Slack plays a role under these conditions.</p><p><strong>Methods and results: </strong>K+ currents in cardiomyocytes (CMs) obtained from wildtype but not from global Slack knockout mice were sensitive to electrical inactivation of voltage-sensitive Na+ channels. Live-cell imaging demonstrated that K+ fluxes across the sarcolemma rely on Slack, while the depolarized resting membrane potential in Slack-deficient CMs led to excessive cytosolic Ca2+ accumulation and finally to hypoxia/reoxygenation-induced cell death. Cardiac damage in an in vivo model of I/R was exacerbated in global and CM-specific conditional Slack mutants and largely insensitive to mechanical conditioning manoeuvres. Finally, the protection conferred by mitochondrial ATP-sensitive K+ (mitoKATP) channels required functional Slack in CMs.</p><p><strong>Conclusion: </strong>Collectively, our study provides evidence for Slack's crucial involvement in the ion homeostasis of no or low O2-stressed CMs. Thereby, Slack activity opposes the I/R-induced fatal Ca2+-uptake to CMs supporting the cardioprotective signaling attributed to mitoKATP function.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"174-189"},"PeriodicalIF":10.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892983","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":"RNA epigenetic modifications: a new field of research in calcific aortic valve disease.","authors":"Mewen Briend, Patrick Mathieu","doi":"10.1093/cvr/cvae256","DOIUrl":"10.1093/cvr/cvae256","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"8-9"},"PeriodicalIF":10.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945171","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":"Mechanisms and consequences of myeloid adhesome dysfunction in atherogenesis.","authors":"Irina Zhevlakova, Huan Liu, Tejasvi Dudiki, Detao Gao, Valentin Yakubenko, Svyatoslav Tkachenko, Olga Cherepanova, Eugene A Podrez, Tatiana V Byzova","doi":"10.1093/cvr/cvae223","DOIUrl":"10.1093/cvr/cvae223","url":null,"abstract":"<p><strong>Aims: </strong>In the context of atherosclerosis, macrophages exposed to oxidized low-density lipoproteins (oxLDLs) exhibit cellular abnormalities, specifically in adhesome functions, yet the mechanisms and implications of these adhesive dysfunctions remain largely unexplored.</p><p><strong>Methods and results: </strong>This study reveals a significant depletion of Kindlin3 (K3) or Fermt3, an essential component of the adhesome regulating integrin functions, in macrophages located within atherosclerotic plaques in vivo and following oxLDL exposure in vitro. To examine the effects of K3 deficiency, the study utilized hyperlipidaemic bone marrow chimeras devoid of myeloid Kindlin3 expression. The absence of myeloid K3 increased atherosclerotic plaque burden in the aortas in vivo and enhanced lipid accumulation and lipoprotein uptake in macrophages from Kindlin3-null chimeric mice in vitro. Importantly, re-expression of K3 in macrophages ameliorated these abnormalities. RNA sequencing of bone marrow-derived macrophages (BMDM) from K3-deficient mice revealed extensive deregulation in adhesion-related pathways, echoing changes observed in wild-type cells treated with oxLDL. Notably, there was an increase in Olr1 expression [encoding the lectin-like oxidized LDL receptor-1 (LOX1)], a gene implicated in atherogenesis. The disrupted K3-integrin axis in macrophages led to a significant elevation in the LOX1 receptor, contributing to increased oxLDL uptake and foam cell formation. Inhibition of LOX1 normalized lipid uptake in Kindlin3-null macrophages. A similar proatherogenic phenotype, marked by increased macrophage LOX1 expression and foam cell formation, was observed in myeloid-specific Itgβ1-deficient mice but not in Itgβ2-deficient mice, underscoring the critical role of K3/Itgβ1 interaction.</p><p><strong>Conclusion: </strong>This study shows that the loss of Kindlin3 in macrophages upon exposure to oxLDL leads to adhesome dysfunction in atherosclerosis and reveals the pivotal role of Kindlin3 in macrophage function and its contribution to the progression of atherosclerosis, providing valuable insights into the molecular mechanisms that could be targeted for therapeutic interventions.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"62-76"},"PeriodicalIF":10.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11999018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406163","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":"Temporal changes in mediation effects on cardiovascular and microvascular outcomes with glucagon-like peptide-1 receptor agonist therapy: a post-hoc analysis of the LEADER trial.","authors":"Zi-Yang Peng, Yu-Hsuan Lee, Huang-Tz Ou, Shihchen Kuo","doi":"10.1093/cvr/cvae237","DOIUrl":"10.1093/cvr/cvae237","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"10-12"},"PeriodicalIF":10.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582134","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":"PINK1-mediated mitophagy attenuates pathological cardiac hypertrophy by suppressing the mtDNA release-activated cGAS-STING pathway.","authors":"Haobin Zhou, Xiao Wang, Tianyu Xu, Daojing Gan, Zhuang Ma, Hao Zhang, Jian Zhang, Qingchun Zeng, Dingli Xu","doi":"10.1093/cvr/cvae238","DOIUrl":"10.1093/cvr/cvae238","url":null,"abstract":"<p><strong>Aims: </strong>Sterile inflammation is implicated in the development of heart failure (HF). Mitochondria play important roles in triggering and maintaining inflammation. Mitophagy is important for regulation of mitochondrial quality and maintenance of cardiac function under pressure overload. The association of mitophagy with inflammation in HF is largely unclear. As PINK1 is a central mediator of mitophagy, our objective was to investigate its involvement in cardiac hypertrophy, and the effect of PINK1-mediated mitophagy on cGAS-STING activation during cardiac hypertrophy.</p><p><strong>Methods and results: </strong>PINK1 knockout and cardiac-specific PINK1-overexpressing transgenic mice were created and subsequently subjected to transverse aortic constriction (TAC) surgery. In order to explore whether PINK1 regulates STING-mediated inflammation during HF, PINK1/STING (stimulator of interferon genes) double-knockout (DKO) mice were created. Pressure overload was induced by TAC. Our findings indicate a significantly decline in PINK1 expression in TAC-induced hypertrophy. Cardiac hypertrophic stimuli caused the release of mitochondrial DNA (mtDNA) into the cytosol, activating the cGAS-STING signalling, which in turn initiated cardiac inflammation and promoted the progression of cardiac hypertrophy. PINK1 deficiency inhibited mitophagy activity, promoted mtDNA release, and then drove the overactivation of cGAS-STING signalling, exacerbating cardiac hypertrophy. Conversely, cardiac-specific PINK1 overexpression protected against hypertrophy thorough inhibition of the cGAS-STING signalling. DKO mice revealed that the effects of PINK1 on hypertrophy were dependent on STING.</p><p><strong>Conclusion: </strong>Our findings suggest that PINK1-mediated mitophagy plays a protective role in pressure overload-induced cardiac hypertrophy via inhibiting the mtDNA-cGAS-STING pathway.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"128-142"},"PeriodicalIF":10.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582132","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":"Beta 2 adrenergic receptor gene methylation activates innate lymphoid cells to drive hypertension in lymphocyte deficient hosts.","authors":"Wei Chen,Sara Perrotta,Liang Xiao,Lorenzo Carnevale,Marwa A Abd-ElDayem,Elizabeth M Hennen,Luis Miguel Rivera-Medina,David M Patrick,Mingfang Ao,Fabio Pallante,Azzurra Zonfrilli,Shilin Zhao,Agnese Migliaccio,Lan Lan,Stefania Fardella,Giuseppe Sciumè,Francesco Mastroiacovo,Giuseppe Lembo,Daniela Carnevale,David G Harrison","doi":"10.1093/cvr/cvaf042","DOIUrl":"https://doi.org/10.1093/cvr/cvaf042","url":null,"abstract":"AIMST cells contribute to hypertension; however, hypertension occurs in settings of T cell deficiency.METHODS AND RESULTSWe studied two colonies of T/B cell-deficient RAG-1-/- mice with disparate responses to angiotensin II, being one protected from blood pressure increase and the other one responsive. This difference depends on the capability of hypertensive RAG-1-/- mice to expand natural killer and innate lymphoid cells (NK/ILCs) that produce pro-hypertensive cytokines. This process is regulated by the DNA methylation status of the β2 adrenergic receptor (β2-AdR). Angiotensin II caused blood pressure elevation in T and NK/ILCs-deficient mice only when either T or NK/ILCs cells were adoptively reconstituted. Additional studies showed NK cell expansion in humans that underwent B cell depletion, and this was augmented in those with hypertension.CONCLUSIONSThese findings illustrate that the modulation of NK/ILCs activation by adrenergic signalling governs an escape mechanism in lymphocyte-deficient host, enabling the development of hypertension.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"183 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818978","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":"Beat strong, think fast: how brain and heart keep each other in check.","authors":"Daniela Carnevale, Costantino Iadecola, Joanna Wardlaw","doi":"10.1093/cvr/cvaf041","DOIUrl":"10.1093/cvr/cvaf041","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"2323-2324"},"PeriodicalIF":10.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779035","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":"Imaging the cerebral vasculature at different scales: translational tools to investigate the neurovascular interfaces.","authors":"Lorenzo Carnevale, Giuseppe Lembo","doi":"10.1093/cvr/cvae165","DOIUrl":"10.1093/cvr/cvae165","url":null,"abstract":"<p><p>The improvements in imaging technology opened up the possibility to investigate the structure and function of cerebral vasculature and the neurovascular unit with unprecedented precision and gaining deep insights not only on the morphology of the vessels but also regarding their function and regulation related to the cerebral activity. In this review, we will dissect the different imaging capabilities regarding the cerebrovascular tree, the neurovascular unit, the haemodynamic response function, and thus, the vascular-neuronal coupling. We will discuss both clinical and preclinical setting, with a final discussion on the current scenery in cerebrovascular imaging where magnetic resonance imaging and multimodal microscopy emerge as the most potent and versatile tools, respectively, in the clinical and preclinical context.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"2373-2384"},"PeriodicalIF":10.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854860","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}