Nature cardiovascular research最新文献

{"title":"Vascular aging as a driver of organ dysfunction and systemic aging","authors":"Stefanie Dimmeler, Hellmut G. Augustin","doi":"10.1038/s44161-026-00883-7","DOIUrl":"10.1038/s44161-026-00883-7","url":null,"abstract":"Centuries ago, Thomas Sydenham famously wrote, “A man is as old as his arteries”, highlighting the importance of the vasculature for health and healthy aging. Here, we review recent developments in vascular aging research, focusing on how microvascular aging drives tissue dysfunction and the emerging therapeutic opportunities for vascular rejuvenation. Although macrovascular aging has long been studied, microvascular aging remains an emerging frontier. Recent single-cell and multiomic technologies now allow unprecedented resolution of vessel wall cellular and molecular heterogeneity across organs throughout life. Beyond angiogenesis, hemodynamics, barrier function, coagulation and inflammation, the vessel wall is increasingly recognized as an instructive gatekeeper of organ function: endothelial and mural cells actively control surrounding parenchyma via angiocrine and pericrine signaling mechanisms, controlling organ function in health and disease. Integrating these technological and conceptual advances has reshaped our understanding of vascular aging, revealing organotypic vulnerabilities and intercellular mechanisms that drive systemic decline. In this Review, Dimmeler and Augustin discuss microvascular aging as an emerging key driver of tissue dysfunction and systemic decline, highlighting how single-cell and multiomic approaches are uncovering organ-specific vascular vulnerabilities and signaling mechanisms, opening new opportunities for vascular rejuvenation and healthy aging.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 10","pages":"926-940"},"PeriodicalIF":12.6,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timed metabolic repair after myocardial infarction","authors":"Chak Kwong Cheng, Yu Huang","doi":"10.1038/s44161-026-00873-9","DOIUrl":"10.1038/s44161-026-00873-9","url":null,"abstract":"After myocardial infarction, injured myocardium enters a highly dynamic metabolic state that is difficult to treat with a single intervention. A study now reports a bioadaptive nanomedicine that sequentially delivers NAD+ and genipin, coordinating mitochondrial protection and metabolic repair to promote functional recovery of the heart.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 10","pages":"914-916"},"PeriodicalIF":12.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteome-wide genetic analyses identify ASGR1 as a potential biomarker linking smoking with ischemic heart disease","authors":"Alexander C. Tinworth, Pang Yao, Andri Iona, Alfred Pozarickij, Adam Von Ende, Iona Y. Millwood, Robin G. Walters, Robert Clarke, Fiona Bragg, Zhengming Chen","doi":"10.1038/s44161-026-00871-x","DOIUrl":"10.1038/s44161-026-00871-x","url":null,"abstract":"Tobacco smoking increases the risk of multiple diseases, but the biological mechanisms involved remain incompletely understood. Here we characterize smoking-related protein profiles to identify potentially causal biomarkers mediating smoking’s effects. In European-ancestry populations, genetically predicted smoking exposures were significantly associated with levels of 93 (total: 2,922) proteins, including higher levels of asialoglycoprotein receptor 1 (ASGR1). The positive association of ASGR1 levels with ischemic heart disease (IHD) was supported by colocalization (posterior probability of hypothesis 4 = 0.91), and was estimated to explain 6.35% (95% confidence interval 2.61–10.09%, P = 8.77 × 10−4) of smoking’s effects on IHD in two-step Mendelian randomization analyses. In network analyses, genetically predicted ASGR1 levels were inversely associated with plasma levels of more than 100 proteins, including growth arrest-specific 6, with all these proteins having rs55714927 (that is, a cis-protein quantitative trait locus for ASGR1) as a trans-protein quantitative trait locus. Sensitivity analyses in never-smokers identified a nonstatistically significant residual association between ASGR1 and IHD, which is consistent with possible horizontal pleiotropy, with body mass index implicated as a potential contributing pathway. Tinworth et al. identify ASGR1 as a potential molecular mediator of smoking-associated risk of ischemic heart disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 10","pages":"999-1015"},"PeriodicalIF":12.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-026-00871-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioadaptive spatiotemporal nanomedicine promotes metabolic recovery after myocardial infarction through NAD+ and UCP2 regulation","authors":"Jue Wang, Yingci Xia, Wenxuan Zheng, Wenqin Yuan, Yunying Huang, Yuntao Zhang, Qiong Huang, Kelong Ai","doi":"10.1038/s44161-026-00874-8","DOIUrl":"10.1038/s44161-026-00874-8","url":null,"abstract":"Myocardial infarction causes persistent mitochondrial and metabolic dysfunction that drives adverse cardiac remodeling. Here we develop NAD+–genipin nanomedicine for metabolic balance (NGB), a physiologically adaptive nanomedicine with staged intracellular release. In a mouse myocardial infarction model, NGB preferentially accumulates in ischemic myocardium, rapidly replenishes nicotinamide adenine dinucleotide (NAD+) and subsequently provides mitochondria-associated sustained NAD+–genipin exposure. This phase-linked delivery limits early mitochondrial stress, apoptosis and inflammation and later restores coordination between oxidative phosphorylation, glycolysis and fatty-acid utilization. Mechanistically, NGB supports sirtuin-1-associated oxidative metabolism and suppresses sustained upregulation of the mitochondrial uncoupling protein 2 (UCP2). In hypoxic cardiomyocytes, UCP2 knockdown plus NAD+ supplementation partially reproduces the NGB metabolic phenotype, whereas UCP2 overexpression and sirtuin 1 inhibition reverse distinct components of NGB-mediated respiratory and glycolytic recovery. NGB thereby reduces fibrosis and ventricular remodeling and preserves cardiac function, supporting temporally coordinated metabolic intervention after myocardial infarction. Wang et al. develop a bioadaptive NAD+–genipin nanomedicine (NGB) that synchronizes early NAD+ replenishment with prolonged mitochondria-targeted metabolic regulation to address the evolving pathology of myocardial infarction. By restoring metabolic homeostasis through coordinated sirtuin 1 and UCP2 signaling, NGB reduced mitochondrial injury, fibrosis and ventricular remodeling while preserving cardiac function in rodent models.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 10","pages":"977-998"},"PeriodicalIF":12.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: CD98hc controls CNS angiogenesis and blood–brain barrier integrity through localized regulation of the systemic integrin–FAK pathway","authors":"Xiaoyan Hu, Min Yu, Shilun Yang, Cheng Fang, Pengju Wei, Xun Zhang, Yinzhong Ma, Ziying Feng, Yukun Chen, Jingyu Yan, Ying Wang, Linhui Qiu, Dengpan Song, Fuyou Guo, Junlei Chang","doi":"10.1038/s44161-026-00888-2","DOIUrl":"10.1038/s44161-026-00888-2","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 10","pages":"1071-1071"},"PeriodicalIF":12.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-026-00888-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk-guided cardioprotection in cardio-oncology","authors":"Kai Yi Wu, Dae Hyun Lee, Ivy S. Han, Laura Barr, Krithika Kuppusamy, Bonnie Ky","doi":"10.1038/s44161-026-00869-5","DOIUrl":"10.1038/s44161-026-00869-5","url":null,"abstract":"The cardiotoxic effects of cancer therapies are well established, and the most clinically relevant consequences include heart failure and cardiomyopathy. As such, efforts have been focused on developing strategies to attenuate the risk of cardiovascular dysfunction in patients receiving potentially cardiotoxic therapies. Randomized trials to identify cardioprotective approaches have largely selected patients on the basis of cancer type and treatment regimen, regardless of baseline or dynamic changes in cardiovascular risk. However, contemporary evidence suggests that this approach results in modest to no significant benefit on subclinical or clinical measures of cardiotoxicity. We hypothesize that a risk-guided cardioprotection approach can enable the delivery of targeted therapy to those who may derive the greatest cardiovascular benefit, avoiding unnecessary treatment of lower-risk populations. Here, we review the contemporary literature on primary cardioprotection and present recent studies in cardio-oncology focused on risk-guided cardioprotection to support the implementation of more tailored strategies. Wu et al. share their perspective on the current limitations of all-comer cardioprotection strategies in cardio-oncology and support the adoption of baseline and dynamic risk stratification to identify patients who may derive the most benefit from cardioprotection.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 10","pages":"917-925"},"PeriodicalIF":12.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148984278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphatic rarefaction drives cardiac inflammaging","authors":"Ebba Brakenhielm, Alma Zernecke","doi":"10.1038/s44161-026-00872-w","DOIUrl":"10.1038/s44161-026-00872-w","url":null,"abstract":"Aging is a major cardiovascular risk factor, but the mechanisms that underlie cardiac inflammaging remain unclear. A study now shows that lymphatic rarefaction is an early determinant of cardiac aging and identifies a VEGF-C– IL-33 signaling axis that regulates lymphatic homeostasis.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 10","pages":"911-913"},"PeriodicalIF":12.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-associated loss of lymphatic vessels promotes cardiac inflammation","authors":"Julian U. G. Wagner, Hamza Gulshan, Ibrahim Sultan, Salli Antila, Laia-Canes Esteve, David Rodriguez Morales, Mariano Ruz Jurado, David John, Emmanouil G. Solomonidis, Katja Schmitz, Josefine Panthel, Haris Kujundzic, Susanne Hille, Oliver J. Müller, Christoph Kugler, Haider Sami, Manfred Ogris, Simone-Franziska Glaser, Wesley T. Abplanalp, Tara Procida-Kowalski, Marek Bartkuhn, Evelyn Ullrich, Marion Muhly-Reinholz, Sarmad Ahmad Khan, Tarik Bozoglu, Christian Kupatt, Florian Buettner, Jochen Pöling, Thomas Braun, Kari Alitalo, Stefanie Dimmeler","doi":"10.1038/s44161-026-00870-y","DOIUrl":"10.1038/s44161-026-00870-y","url":null,"abstract":"Aging is a major risk factor for cardiovascular disease, but the role of the cardiac lymphatic vasculature in this process remains poorly understood. Here we show that aging reduces cardiac lymphatic vessel density in humans and mice and induces structural remodeling characterized by tighter, zipper-like endothelial junctions. These changes are associated with immune cell infiltration, fibrinogen and amyloid accumulation, and myocardial edema. Selective reduction of cardiac lymphatics in young mice, through Flt4 (VEGFR3) depletion or soluble Flt4 overexpression, recapitulates key features of cardiac aging, including inflammation and impaired lymphatic integrity. Mechanistically, aging induces selective upregulation of nuclear interleukin-33 (IL-33) in lymphatic endothelial cells. Unlike extracellular IL-33, nuclear IL-33 promotes lymphatic endothelial cell death and junctional remodeling. We identify VEGFC as an age-sensitive regulator that declines with aging and suppresses IL-33. Cardiac Vegfc overexpression or Il33 silencing restores lymphatic density and tissue homeostasis in aged hearts, identifying a potential therapeutic target for age-related cardiac dysfunction. Wagner et al. reveal that age-related impairment of lymphatic integrity is driven by increased nuclear interleukin-33 expression in lymphatic endothelial cells and can be counteracted by cardiac Vegfc overexpression.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 10","pages":"961-976"},"PeriodicalIF":12.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-026-00870-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial mapping and functional genomics show how mouse cardiomyocytes mature","authors":"","doi":"10.1038/s44161-026-00862-y","DOIUrl":"10.1038/s44161-026-00862-y","url":null,"abstract":"Integration of single-nucleus and spatial transcriptomics defined the cellular niches and regulatory networks that orchestrate postnatal cardiomyocyte maturation. Scalable in vivo perturbation by PIP-seq identified 21 regulators of structural, metabolic and electrophysiological maturation of the postnatal heart.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 9","pages":"793-794"},"PeriodicalIF":12.6,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artery tertiary lymphoid organs encode a pathogenic high-affinity autoantibody−autoantigen pair in atherosclerosis","authors":"Chuankai Zhang, Xi Zhang, Yi Ran, Zhihua Wang, Liping Li, Shu Wang, Junjie Zheng, Yixin Zhang, Ting Sun, Yutao Li, Shu Lu, Mingyang Hong, Zhe Ma, Sabine Steffens, Michael Hristov, Xavier Blanchet, Jingpu Zhu, Xinwen Dou, Xinyi Deng, Klaus Dornmair, Desheng Hu, Shibojyoti Lahiri, Axel Imhof, Nadja Sachs, Lars Maegdefessel, Jingyi Xiao, Jianning Zhang, Yan Wang, Hua Hong, Livia Habenicht, Xinyu Weng, Junbo Ge, Christian Weber, Donato Santovito, Rachael Bashford-Rogers, Sarajo K. Mohanta, Klaus Ley, Andreas J. R. Habenicht, Changjun Yin","doi":"10.1038/s44161-026-00864-w","DOIUrl":"10.1038/s44161-026-00864-w","url":null,"abstract":"Artery tertiary lymphoid organs (ATLOs) emerge in atherosclerosis, which is a chronic inflammatory artery disease with an autoimmune component. However, whether disease-relevant autoimmune B cells emerge in ATLOs remains unknown. In this study, we isolate germinal center (GC) B cells from ATLOs and lymph nodes from healthy and atherosclerosis-burdened mice, expression clone 60 autoantibodies and screen them for arterial wall reactivity. ATLO GC B cell-derived autoantibodies skew to atherosclerosis-relevant autoantigens versus their counterparts in lymph nodes of both genotypes. One ATLO GC B cell-derived autoantibody (termed A6) binds to histone 2B (H2B) with high affinity. Both vaccination with H2B and adoptive transfer of A6 accelerate atherosclerosis, revealing a pathogenic autoantibody−autoantigen pair. Mechanistically, ATLOs specifically show both distorted B cell activation and immune tolerance checkpoint-regulating gene expression profiles. In a human cohort, circulating anti-H2B antibody titers positively correlate with aortic calcification in humans. We suggest that ATLOs harbor a dysregulated immune tolerance environment permissive for autoreactive B cells that express pathogenic autoantibodies promoting atherosclerosis. By combining single-cell transcriptomic and B cell receptor sequencing of germinal center B cells within artery tertiary lymphoid organs, Zhang, Zhang, Ran, Wang et al. identify and clone an autoreactive monoclonal antibody A6 targeting histone 2B (H2B) and demonstrate that both H2B vaccination and adoptive transfer of the anti-H2B A6 monoclonal antibody significantly accelerated atherosclerosis progression.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 9","pages":"869-890"},"PeriodicalIF":12.6,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-026-00864-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}