Cardiovascular Research最新文献

{"title":"Mapping disease-specific vascular cell populations responsible for obliterative arterial remodeling during development of pulmonary arterial hypertension","authors":"Nicholas D Cober, Emma McCourt, Rafael Soares Godoy, Yupu Deng, Ken Schlosser, Elmira Safaie Qamsari, Jalil Azami, Elham Salehisiavashani, David P Cook, Sarah-Eve Lemay, Timothy Klouda, Ke Yuan, Sébastien Bonnet, Duncan J Stewart","doi":"10.1093/cvr/cvaf146","DOIUrl":"https://doi.org/10.1093/cvr/cvaf146","url":null,"abstract":"Background Pulmonary arterial hypertension (PAH) is a lethal pulmonary vascular disease characterized by arteriolar pruning and occlusive vascular remodeling leading to increased pulmonary vascular resistance and eventually right heart failure. While endothelial cell (EC) injury and apoptosis are known triggers for this disease, the mechanisms by which they lead to complex arterial remodeling remain obscure. Aims We employed multiplexed single-cell RNA sequencing at multiple timepoints during the onset and progression of disease in a model of severe PAH to identify mechanisms involved in the development of occlusive arterial lesions. Methods and Results Single cell transcriptional analysis resolved 44 global lung cell populations, with widespread early transcriptomic changes at 1 week affecting endothelial, stromal and immune cell populations. In particular, two EC clusters were greatly expanded during PAH development and were identified as being disease specific: a relatively dedifferentiated (dD) EC population that was enriched for Cd74 expression while exhibiting a loss of endothelial identity; and an activated arterial EC (aAEC) population that uniquely exhibited persistent differential gene expression throughout PAH development consistent with a growth regulated state. dDECs were primed to undergo endothelial-mesenchymal transition as evidenced by reduced activity of master EC transcription factors, Erg and Fli1, and further supported by RNA velocity analysis showing vectors leading to fibroblast clusters. Of note, aAECs exhibited high expression of Tm4sf1, a gene implicated in cancer cell growth, that was also expressed by a smooth muscle (SM)-like pericyte cluster, and were highly localized to regions of arterial remodeling in both the rat model and PAH patients, contributing to intimal occlusive lesions and SM-like pericytes forming bands of medial muscularization. Conclusions Together these findings implicate disease-specific vascular cells in PAH progression and suggest that TM4SF1 may be a novel therapeutic target for arterial remodeling. Translational Perspectives Using single cell transcriptomic analysis in both human lung samples and a rat model of severe PAH we have identified disease-specific EC populations contributing to complex arterial remodeling, including growth-dysregulated, activated arterial ECs (aAECs) and dedifferentiated ECs (dDECs) that may be primed for endothelial to mesenchymal transition. In particular, aAECs exhibit high expression of a surface marker, TM4SF1, which is essential for their hyper-proliferative phenotype and represents a promising therapeutic target for RNA silencing approaches or as an antigen to guide immune-mediated ablation of this cancer-like EC population in PAH.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"27 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915746","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":"Cardiac ageing: from hallmarks to therapeutic opportunities.","authors":"Margaret H Hastings, Qiulian Zhou, Chao Wu, Parisa Shabani, Shengyuan Huang, Xuejing Yu, Anand P Singh, J Sawalla Guseh, Haobo Li, Carolin Lerchenmüller, Anthony Rosenzweig","doi":"10.1093/cvr/cvae124","DOIUrl":"10.1093/cvr/cvae124","url":null,"abstract":"<p><p>Cardiac ageing is an intricate and multifaceted process with considerable impact on public health, especially given the global demographic shift towards aged populations. This review discusses structural, cellular, and functional changes associated with cardiac ageing and heart failure with preserved ejection fraction (HFpEF). Key molecular mediators are considered within the framework of the established hallmarks of ageing, with particular attention to promising therapeutic candidates. We further delineate the differential impacts of ageing on cardiac structure and function in men and women, addressing hormonal and chromosomal influences. The protective and mitigating effects of exercise in cardiac ageing and HFpEF in particular are discussed, as an inspiration for the identification of pathways that mitigate biological ageing. We also emphasize how much remains to be learned and the importance of these efforts in enhancing the cardiac health of ageing populations worldwide.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1474-1488"},"PeriodicalIF":13.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449777","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":"Rethinking cardiovascular ageing.","authors":"Patrick Lacolley, María Mittelbrunn, Stefanie Dimmeler","doi":"10.1093/cvr/cvaf140","DOIUrl":"10.1093/cvr/cvaf140","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1465-1467"},"PeriodicalIF":13.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834084","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":"Beneficial effects of vascular endothelial growth factor B gene transfer in the aged heart.","authors":"Nivethitha Manickam, Ibrahim Sultan, Josefine Panthel, Haris Kujundzic, Ariane Fischer, Katja Schmitz, Mariano Ruz Jurado, David Rodriguez Morales, David John, Simone-Franziska Glaser, Kathrin A Stilz, Pedro Felipe Malacarne, Ralf Peter Brandes, Thomas Braun, Carolin Lerchenmüller, Fynn Betge, Wesley T Abplanalp, Kari Alitalo, Stefanie Dimmeler, Julian U G Wagner","doi":"10.1093/cvr/cvaf046","DOIUrl":"10.1093/cvr/cvaf046","url":null,"abstract":"<p><strong>Aims: </strong>Members of the VEGF family are crucial modulators of vascular and neural function. While VEGFA signalling has been shown to mitigate several aging-related cardiac phenotypes and prolong survival in aged mice, the role of VEGFB in cardiac aging remains underexplored. In this study, we identify a significant decline in Vegfb expression, particularly of its soluble isoform Vegfb186, in aged mouse and human hearts. To assess the therapeutic potential of VEGFB in aging-associated cardiac pathologies, we used AAV9-mediated gene transfer to overexpress Vegfb186 in 18-month-old male C57Bl/6J mice.</p><p><strong>Methods and results: </strong>VEGFB is known to exhibit vascular and neuroprotective effects that we assessed in the ageing heart. In the aged heart, doses of Vegfb186 overexpression that had only a modest effect on the vascular endothelium prevented age-induced diastolic dysfunction and fibrosis. Vegfb186 treatment additionally restored sympathetic and sensory nerve fibre density and increased heart rate variability. Although Vegfb186 overexpression induced cardiac hypertrophy, our findings indicated that this hypertrophy was compensatory rather than pathological as Vegfb186 overexpression corrected the elevated cardiomyocyte length-to-width ratio observed in aged hearts, a metric typically indicative of pathological remodelling. Cardiac single-nucleus RNA sequencing of the hearts and in vitro analysis of the cardiomyocytes indicated up-regulation of the STAT3 signal transduction pathway as a potential contributor of VEGFB-induced cardiac hypertrophy.</p><p><strong>Conclusion: </strong>Our findings demonstrate that Vegfb186 overexpression partially reverses age-related cardiac pathologies such as diastolic dysfunction and fibrosis. This work highlights VEGFB as a potential therapeutic target for combating cardiac aging and its associated dysfunctions.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1594-1608"},"PeriodicalIF":13.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673282","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":"Lamin: guardian against DNA damage by transcription stress.","authors":"James W S Jahng, Joseph C Wu","doi":"10.1093/cvr/cvae122","DOIUrl":"10.1093/cvr/cvae122","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1468-1470"},"PeriodicalIF":13.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417909","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":"Anti-ageing interventions for the treatment of cardiovascular disease.","authors":"Mahmoud Abdellatif, Sophie T Schmid, Alexander Fuerlinger, Guido Kroemer","doi":"10.1093/cvr/cvae177","DOIUrl":"10.1093/cvr/cvae177","url":null,"abstract":"<p><p>As the global demographic landscape continues to shift towards an aged population, so does the medical and socioeconomic burden of cardiovascular diseases. Indeed, ageing is one of, if not, the key risk factor for the development of cardiovascular diseases. However, there are currently no approved cardiovascular therapeutics that primarily target the molecular and cellular mechanisms underlying the ageing process itself. In this review, we present the potential of emerging anti-ageing strategies, including epigenetic rejuvenation, metabolic reprogramming, autophagy activation, as well as senolytic and anti-inflammatory therapies, in delaying or reversing the development of age-related cardiovascular disorders, while considering potential sex differences. In doing so, we implicate cellular ageing processes in the pathogenesis of several prevalent cardiovascular diseases, such as atherosclerosis, hypertension, various types of cardiomyopathies (including its hypertrophic, ischaemic, dilated, diabetic, and arrhythmogenic forms) and heart failure, particularly that with preserved ejection fraction. Finally, we outline future challenges and steps needed for the implementation of these novel anti-ageing strategies in the clinical setting, with the aim of challenging the long-held notion of ageing as a 'non-modifiable' risk factor for cardiovascular diseases.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1524-1536"},"PeriodicalIF":13.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035339","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":"Aging in the vascular system: lessons from mechanobiology, computational approaches, and oxidative stress.","authors":"Patrick Lacolley, Stéphane Avril, Tamás Gáll, György Balla, Jozsef Balla, Jean-Baptiste Michel, Véronique Regnault","doi":"10.1093/cvr/cvaf137","DOIUrl":"10.1093/cvr/cvaf137","url":null,"abstract":"<p><p>Vascular aging is considered now to be the first factor of multiorgan aging in what is called 'the vascular theory of aging'. Clinical understanding of vascular aging has long been limited to arterial hypertension and arterial stiffness. The effects of age on arterial mechanical properties have always been difficult to interpret for reasons linked to the non-linear behaviour of the stiffness/pressure function and the complex interactions between vascular cells and the matrix. Even new methodologies for decoding aging at the single-cell level are equally difficult to interpret. The objectives of this review are: (i) to introduce new computational approaches in biomechanics and mechanobiology; (ii) to revisit the role of oxidative stress and cellular senescence; (iii) to summarize some of the main molecular, cellular, and mechanistic contributions to vascular aging; (iv) to present the latest human studies of accelerated arterial aging with particular reference to cognitive impairment and functional decline; and (v) to propose some future directions for research related to vascular aging.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1566-1581"},"PeriodicalIF":13.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844533","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":"How to measure and model cardiovascular aging","authors":"Luke Spray, Gavin Richardson, Laura K Booth, Judith Haendeler, Joachim Altschmied, Daniel I Bromage, Sienna B Wallis, Konstantinos Stellos, Simon Tual-Chalot, Ioakim Spyridopoulos","doi":"10.1093/cvr/cvaf138","DOIUrl":"https://doi.org/10.1093/cvr/cvaf138","url":null,"abstract":"Most acquired cardiovascular diseases are more common in older people, and the biological mechanisms and manifestations of aging provide insight into cardiovascular pathophysiology. Measuring aging within the cardiovascular system may help to better understand risk profiles for specific individuals and direct targeted preventative therapy. In this review, we explore telomere attrition, cellular senescence, epigenetic modifications, and mitochondrial dysfunction as key molecular mechanisms of aging. These phenomena are associated with cardiovascular disease through endothelial dysfunction and systemic inflammation, which are measurable in clinical practice with a variety of clinical, laboratory, and imaging techniques. Finally, we discuss that the next tools for modelling cardiovascular aging must be capable of incorporating a vast amount of diverse data from a given patient, pointing to recent developments in artificial intelligence and machine learning.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"15 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910858","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 \"second hit\" mouse model for group 2 and 3 pulmonary hypertension: Combination of aortic banding and hypoxia exposure.","authors":"Laura K Pallos, Michaela Matthey, Michael Hesse, Bernd K Fleischmann, Wilhelm Röll, Daniela Wenzel","doi":"10.1093/cvr/cvaf147","DOIUrl":"https://doi.org/10.1093/cvr/cvaf147","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944107","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":"Pro-inflammatory monocytes in patients with calcific aortic valve disease.","authors":"Wieteke Broeders, Amber van Broekhoven, Aysun Cetinyurek-Yavuz, Erwin Zegers, Anthonie L Duijnhouwer, Mihai G Netea, Siroon Bekkering, Niels van Royen, Saloua El Messaoudi, Niels P Riksen","doi":"10.1093/cvr/cvaf148","DOIUrl":"https://doi.org/10.1093/cvr/cvaf148","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944163","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}