Nature cardiovascular research最新文献_第5页

CD248⁺ fibroblasts drive cardiac fibrosis by interacting with immune cells. CD248+成纤维细胞通过与免疫细胞相互作用驱动心脏纤维化。

IF 9.4

Nature cardiovascular research Pub Date : 2025-04-01 DOI: 10.1038/s44161-025-00625-1

引用次数: 0

Single-nucleus multi-omics implicates androgen receptor signaling in cardiomyocytes and NR4A1 regulation in fibroblasts during atrial fibrillation. 单核多组学涉及心房颤动期间心肌细胞中的雄激素受体信号和成纤维细胞中的NR4A1调节。

IF 9.4

Nature cardiovascular research Pub Date : 2025-04-01 Epub Date: 2025-03-25 DOI: 10.1038/s44161-025-00626-0

Francis J A Leblanc, Chi Him Kendrick Yiu, Lucia M Moreira, Aaron M Johnston, Neelam Mehta, Antonios Kourliouros, Rana Sayeed, Stanley Nattel, Svetlana Reilly, Guillaume Lettre

{"title":"Single-nucleus multi-omics implicates androgen receptor signaling in cardiomyocytes and NR4A1 regulation in fibroblasts during atrial fibrillation.","authors":"Francis J A Leblanc, Chi Him Kendrick Yiu, Lucia M Moreira, Aaron M Johnston, Neelam Mehta, Antonios Kourliouros, Rana Sayeed, Stanley Nattel, Svetlana Reilly, Guillaume Lettre","doi":"10.1038/s44161-025-00626-0","DOIUrl":"10.1038/s44161-025-00626-0","url":null,"abstract":"The dysregulation of gene expression programs in the human atria during persistent atrial fibrillation (AF) is not completely understood. Here, we reanalyze bulk RNA-sequencing datasets from two studies (N = 242) and identified 755 differentially expressed genes in left atrial appendages of individuals with persistent AF and non-AF controls. We combined the bulk RNA-sequencing differentially expressed genes with a left atrial appendage single-nucleus multi-omics dataset to assign genes to specific atrial cell types. We found noncoding genes at the IFNG locus (LINC01479, IFNG-AS1) strongly dysregulated in cardiomyocytes. We defined a gene expression signature potentially driven by androgen receptor signaling in cardiomyocytes from individuals with AF. Cell-type-specific gene expression modules suggested an increase in T cell and a decrease in adipocyte and neuronal cell gene expression in AF. Lastly, we showed that reducing NR4A1 expression, a marker of a poorly characterized human atrial fibroblast subtype, fibroblast activation markers, extracellular matrix remodeling and cell proliferation decreased.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":"433-444"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712433","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}

引用次数: 0

Dynamic molecular atlas of cardiac fibrosis at single-cell resolution shows CD248 in cardiac fibroblasts orchestrates interactions with immune cells. 单细胞分辨率心脏纤维化动态分子图谱显示，心脏成纤维细胞中的CD248协调与免疫细胞的相互作用。

IF 9.4

Nature cardiovascular research Pub Date : 2025-04-01 Epub Date: 2025-03-27 DOI: 10.1038/s44161-025-00617-1

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

{"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.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":"380-396"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","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}

引用次数: 0

Inflammatory CD248⁺ activated fibroblasts are a potential therapeutic target in ischemic heart disease. 炎性CD248+激活的成纤维细胞是缺血性心脏病的潜在治疗靶点。

IF 9.4

Nature cardiovascular research Pub Date : 2025-04-01 DOI: 10.1038/s44161-025-00632-2

Joel G Rurik

引用次数: 0

Genetic tracing and topography of spontaneous and stimulated cardiac regeneration in mice. 小鼠自发和刺激心脏再生的基因追踪和地形。

IF 9.4

Nature cardiovascular research Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1038/s44161-025-00623-3

Ilaria Secco, Ana Backovic, Mateusz Tomczyk, Antonio Mura, Gang Li, Francesca Bortolotti, Simone Vodret, Matteo Dal Ferro, Elena Chiavacci, Lorena Zentilin, Gianfranco Sinagra, Serena Zacchigna, Miguel Mano, Mauro Giacca

{"title":"Genetic tracing and topography of spontaneous and stimulated cardiac regeneration in mice.","authors":"Ilaria Secco, Ana Backovic, Mateusz Tomczyk, Antonio Mura, Gang Li, Francesca Bortolotti, Simone Vodret, Matteo Dal Ferro, Elena Chiavacci, Lorena Zentilin, Gianfranco Sinagra, Serena Zacchigna, Miguel Mano, Mauro Giacca","doi":"10.1038/s44161-025-00623-3","DOIUrl":"10.1038/s44161-025-00623-3","url":null,"abstract":"Despite recent efforts to stimulate endogenous cardiomyocyte proliferation for cardiac regeneration, the lack of reliable in vivo methods for monitoring cardiomyocyte replication has hindered our understanding of its mechanisms. Thymidine analogs, used to label proliferating cells, are unsuitable for long-term cardiac regeneration studies as their DNA incorporation elicits a damage response, leading to their elimination. Here we present CycleTrack, a genetic strategy based on the transcriptional activation of Cre recombinase from a temporally regulated cyclin B2 promoter segment, for permanent labeling of cardiomyocytes passing through the G2/M phase. Using CycleTrack, we visualized cardiomyocyte turnover in neonatal and adult mice under various conditions, including pregnancy, increased ventricular afterload, and myocardial infarction. CycleTrack also provided visual and quantitative evidence of ventricular remuscularization following treatment with pro-regenerative microRNAs. We identify the subendocardium as a key site of mitotic activity and provide a mode of cardiomyocyte division along their short axis. CycleTrack is a powerful tool to monitor cardiomyocyte renewal during regenerative interventions.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":"397-411"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588442","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}

引用次数: 0

Machine learning-assisted cell-free DNA screening predicts pre-eclampsia risk. 机器学习辅助无细胞DNA筛查预测先兆子痫风险。

IF 9.4

Nature cardiovascular research Pub Date : 2025-04-01 DOI: 10.1038/s44161-025-00647-9

Andrea Tavosanis

引用次数: 0

27-hydroxycholesterol and endothelial cell immune memory link maternal hypercholesterolemia with atherosclerosis in the offspring. 27-羟基胆固醇和内皮细胞免疫记忆将母体高胆固醇血症与后代动脉粥样硬化联系起来。

IF 9.4

Nature cardiovascular research Pub Date : 2025-04-01 DOI: 10.1038/s44161-025-00631-3

Chieko Mineo, Philip W Shaul

引用次数: 0

Epigenetic silencing of PCSK9 enables durable reduction of low-density lipoprotein cholesterol. PCSK9的表观遗传沉默能够持久地降低低密度脂蛋白胆固醇。

IF 9.4

Nature cardiovascular research Pub Date : 2025-04-01 DOI: 10.1038/s44161-025-00644-y

Elisa Martini

引用次数: 0

Single-cell RNA sequencing reveals sex differences in the subcellular composition and associated gene-regulatory network activity of human carotid plaques. 单细胞RNA测序揭示了人类颈动脉斑块亚细胞组成和相关基因调控网络活性的性别差异。

IF 9.4

Nature cardiovascular research Pub Date : 2025-04-01 Epub Date: 2025-04-10 DOI: 10.1038/s44161-025-00628-y

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

{"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":"https://doi.org/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.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 4","pages":"412-432"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","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}

引用次数: 0

The immune checkpoint regulator CD40 potentiates myocardial inflammation. 免疫检查点调节因子CD40增强心肌炎症。

IF 9.4

Nature cardiovascular research Pub Date : 2025-04-01 Epub Date: 2025-04-11 DOI: 10.1038/s44161-025-00633-1

Jesus Jimenez, Junedh Amrute, Pan Ma, Xiaoran Wang, Shibali Das, Raymond Dai, Yohei Komaru, Andreas Herrlich, Matthias Mack, Kory J Lavine

{"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":"https://doi.org/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.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 4","pages":"458-472"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","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}

引用次数: 0