Nature cardiovascular research最新文献

{"title":"A perspective on thrombogenesis through gut microbiota-derived bile acids and platelet activation","authors":"Cristina Menni, Ana M. Valdes","doi":"10.1038/s44161-025-00634-0","DOIUrl":"10.1038/s44161-025-00634-0","url":null,"abstract":"Cardiovascular arterial thrombosis poses a major health burden, despite intensive antiplatelet therapy, and platelet hyper-reactivity drives thrombus formation, yet its molecular mechanisms remain unknown. A study now shows that gut microbiota–derived deoxycholic acid modulates platelet activity and thrombosis risk in coronary artery disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 5","pages":"505-507"},"PeriodicalIF":10.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044421","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":"The gut microbiota–bile acid–TGR5 axis orchestrates platelet activation and atherothrombosis","authors":"Zhiyong Qi, Wei Zhang, Peng Zhang, Yanan Qu, Haoxuan Zhong, Luning Zhou, Wenxuan Zhou, Wenlong Yang, Huajie Xu, Xin Zhao, Hongyi Wu, Juying Qian, Junbo Ge","doi":"10.1038/s44161-025-00637-x","DOIUrl":"10.1038/s44161-025-00637-x","url":null,"abstract":"Gut microbiota-derived bile acids are crucial in the pathogenesis and treatment of metabolic diseases. However, their impact on platelet activation and thrombosis in coronary artery disease (CAD) remains poorly understood. In this study, we observed reduced serum deoxycholic acid (DCA) in patients with CAD and an underrepresentation of Bacteroides vulgatus in the gut microbiota of patients with CAD, affecting DCA metabolism. We used Takeda G-protein-coupled receptor 5 (TGR5) inhibitors and TGR5 knockout mice to show that DCA inhibited agonist-induced platelet activation and thrombosis by interacting with the platelet TGR5. Oral gavage treatments with DCA, B. vulgatus and stool from healthy individuals suppressed platelet hyperreactivity and thrombosis in atherosclerotic ApoE−/− mice, reduced microvascular thrombosis and protected the heart from myocardial ischemia/reperfusion injury. Here we describe the role of the bile acid DCA in platelet activation and suggest that targeting the gut microbiota and/or altering bile acid metabolism may be beneficial to treat CAD-associated thrombosis. Qi et al. show that bile acids produced by the gut microbiota can suppress platelet activation and reduce atherothrombosis, protecting atherosclerotic mice from myocardial ischemia/reperfusion injury.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 5","pages":"584-601"},"PeriodicalIF":10.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030280","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":"The immune checkpoint regulator CD40 potentiates myocardial inflammation","authors":"Jesus Jimenez, Junedh Amrute, Pan Ma, Xiaoran Wang, Shibali Das, Raymond Dai, Yohei Komaru, Andreas Herrlich, Matthias Mack, Kory J. Lavine","doi":"10.1038/s44161-025-00633-1","DOIUrl":"10.1038/s44161-025-00633-1","url":null,"abstract":"Immune checkpoint therapeutics including CD40 agonists have tremendous promise to elicit antitumor responses in patients resistant to current therapies. Conventional immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 antagonists) are associated with serious adverse cardiac events including life-threatening myocarditis. However, little is known regarding the potential for CD40 agonists to trigger myocardial inflammation or myocarditis. Here we leverage genetic mouse models, single-cell sequencing and cell depletion studies to show that an anti-CD40 agonist antibody reshapes the cardiac immune landscape through activation of CCR2+ macrophages and subsequent recruitment of effector memory CD8+ T cells. We identify a positive feedback loop between CCR2+ macrophages (positive for the chemokine receptor CCR2) and CD8+ T cells driven by IL-12b, TNF and IFNγ signaling that promotes myocardial inflammation and show that previous exposure to CD40 agonists sensitizes the heart to secondary insults and accelerates left ventricular remodeling. Collectively, these findings highlight the potential for CD40 agonists to promote myocardial inflammation and potentiate heart failure pathogenesis. Jimenez et al. show that CD40 agonists can induce myocardial inflammation by activating cardiac macrophages and CD8+ T cells, sensitizing the heart to secondary injury and promoting adverse remodeling.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 4","pages":"458-472"},"PeriodicalIF":10.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057990","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":"Sex and the Garden of Eden","authors":"Peter Libby, Michael C. Honigberg, Amélie Vromman","doi":"10.1038/s44161-025-00624-2","DOIUrl":"10.1038/s44161-025-00624-2","url":null,"abstract":"Despite only one chromosome differing between men and women, sex makes an enormous difference in clinical cardiovascular diseases. Recent multi-omic data expand our understanding of the underlying mechanisms that may contribute to this disparity in humans.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 4","pages":"356-357"},"PeriodicalIF":10.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031788","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":"Single-cell RNA sequencing reveals sex differences in the subcellular composition and associated gene-regulatory network activity of human carotid plaques","authors":"Katyayani Sukhavasi, Giuseppe Mocci, Lijiang Ma, Chani J. Hodonsky, Ernest Diez Benevante, Lars Muhl, Jianping Liu, Sonja Gustafsson, Byambajav Buyandelger, Simon Koplev, Urban Lendahl, Michael Vanlandewijck, Prosanta Singha, Tiit Örd, Mustafa Beter, Ilakya Selvarajan, Johanna P. Laakkonen, Marika Väli, Hester M. den Ruijter, Mete Civelek, Ke Hao, Arno Ruusalepp, Christer Betsholtz, Heli Järve, Jason C. Kovacic, Clint L. Miller, Casey Romanoski, Minna U. Kaikkonen, Johan L. M. Björkegren","doi":"10.1038/s44161-025-00628-y","DOIUrl":"10.1038/s44161-025-00628-y","url":null,"abstract":"Carotid stenosis causes ischemic stroke in both sexes, but the clinical presentation and plaque characteristics differ. Here we run deep single-cell sequencing of 7,690 human carotid plaque cells from male and female patients. While we found no sex differences in major cell types, we identified a predominance of the osteogenic phenotype in smooth muscle cells, immunomodulating macrophages (MPs) and endothelial cells (ECs) undergoing endothelial-to-mesenchymal transition in females. In males, we found smooth muscle cells with the chondrocytic phenotype, MPs involved in tissue remodeling and ECs with angiogenic activity. Sex-biased subcellular clusters were integrated with tissue-specific gene-regulatory networks (GRNs) from the Stockholm–Tartu Atherosclerosis Reverse Network Engineering Task study. We identified GRN195 involved in angiogenesis and T cell-mediated cytotoxicity in male ECs, while in females, we found GRN33 and GRN122 related to TREM2−/TREM1+ MPs and endothelial-to-mesenchymal transition. The impact of GRN195 on EC proliferation in males was functionally validated, providing evidence for potential therapy targets for atherosclerosis that are sex specific. Using deep sequencing of human carotid plaque cells from male and female patients with carotid stenosis, Sukhavasi et al. identify sex-biased cell-type-specific gene-regulatory networks and different phenotypes in smooth muscle cells, including an osteogenic phenotype in females and a chondrocytic phenotype in males.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 4","pages":"412-432"},"PeriodicalIF":10.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060183","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":"Machine learning-assisted cell-free DNA screening predicts pre-eclampsia risk","authors":"Andrea Tavosanis","doi":"10.1038/s44161-025-00647-9","DOIUrl":"10.1038/s44161-025-00647-9","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 4","pages":"348-348"},"PeriodicalIF":10.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812968","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":"Epigenetic silencing of PCSK9 enables durable reduction of low-density lipoprotein cholesterol","authors":"Elisa Martini","doi":"10.1038/s44161-025-00644-y","DOIUrl":"10.1038/s44161-025-00644-y","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 4","pages":"347-347"},"PeriodicalIF":10.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812965","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":"Left ventricular entry during catheter ablation reduces risk of brain lesions","authors":"Xiulin Koehler","doi":"10.1038/s44161-025-00646-w","DOIUrl":"10.1038/s44161-025-00646-w","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 4","pages":"349-349"},"PeriodicalIF":10.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782085","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":"CD248+ fibroblasts drive cardiac fibrosis by interacting with immune cells","authors":"","doi":"10.1038/s44161-025-00625-1","DOIUrl":"10.1038/s44161-025-00625-1","url":null,"abstract":"A unique subset of cardiac fibroblasts expressing CD248 orchestrates immune–fibroblast crosstalk, promoting chronic cardiac fibrosis and dysfunction after ischemia–reperfusion injury, with potential implications for therapeutic intervention.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 4","pages":"358-359"},"PeriodicalIF":10.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733459","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":"Dynamic molecular atlas of cardiac fibrosis at single-cell resolution shows CD248 in cardiac fibroblasts orchestrates interactions with immune cells","authors":"Guohua Li, Cheng Ni, Jiacheng Wang, Feimu Zhang, Zaiyang Fu, Lingjun Wang, Biqing Wang, Ye Liu, Jing Zhao, Mo Li, Hao Lin, Fei Liao, Shuchang Ye, Yu Zhang, Jiayue Cai, Shaohui Shi, Zhiwei Zhong, Yanna Shi, Junhua He, Xushen Xiong, Yang Xu, Jinghai Chen, Wei Zhu, Yibin Wang, Jian’an Wang, Xinyang Hu","doi":"10.1038/s44161-025-00617-1","DOIUrl":"10.1038/s44161-025-00617-1","url":null,"abstract":"Post-injury remodeling is a complex process involving temporal specific cellular interactions in the injured tissue where the resident fibroblasts play multiple roles. Here, we performed single-cell and spatial transcriptome analysis in human and mouse infarcted hearts to dissect the molecular basis of these interactions. We identified a unique fibroblast subset with high CD248 expression, strongly associated with extracellular matrix remodeling. Genetic Cd248 deletion in fibroblasts mitigated cardiac fibrosis and dysfunction following ischemia/reperfusion. Mechanistically, CD248 stabilizes type I transforming growth factor beta receptor and thus upregulates fibroblast ACKR3 expression, leading to enhanced T cell retention. This CD248-mediated fibroblast–T cell interaction is required to sustain fibroblast activation and scar expansion. Disrupting this interaction using monoclonal antibody or chimeric antigen receptor T cell reduces T cell infiltration and consequently ameliorates cardiac fibrosis and dysfunction. Our findings reveal a CD248+ fibroblast subpopulation as a key regulator of immune–fibroblast cross–talk and a potential therapy to treat tissue fibrosis. Using single-cell and spatial molecular profiling of infarcted mouse and human hearts, Li, Ni, Wang and colleagues identify a subset of cardiac fibroblasts expressing CD248 that plays a critical role in fibroblast–T cell interaction, and show that disrupting this interaction with monoclonal antibodies or anti-CD248 chimeric antigen receptor T cells results in reduced cardiac fibrosis and improved function.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 4","pages":"380-396"},"PeriodicalIF":10.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733461","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}