Nature cardiovascular research最新文献_第2页

Low-dose interleukin-2 induces clonal expansion of BACH2-repressed effector regulatory T cells following acute coronary syndrome. 低剂量白介素-2诱导急性冠脉综合征后bach2抑制效应调节性T细胞克隆扩增

IF 9.4

Nature cardiovascular research Pub Date : 2025-06-03 DOI: 10.1038/s44161-025-00652-y

A G Case, J W O'Brien, Y Lu, F T W Charlier, X Zhao, Y Weng, L Masters, Z K Tuong, R Sriranjan, J Cheriyan, C Kemper, M R Clatworthy, Z Mallat, T X Zhao

{"title":"Low-dose interleukin-2 induces clonal expansion of BACH2-repressed effector regulatory T cells following acute coronary syndrome.","authors":"A G Case, J W O'Brien, Y Lu, F T W Charlier, X Zhao, Y Weng, L Masters, Z K Tuong, R Sriranjan, J Cheriyan, C Kemper, M R Clatworthy, Z Mallat, T X Zhao","doi":"10.1038/s44161-025-00652-y","DOIUrl":"https://doi.org/10.1038/s44161-025-00652-y","url":null,"abstract":"Targeting inflammation in atherosclerotic cardiovascular disease remains a major unmet need. Low-dose interleukin-2 (IL-2LD) selectively increases regulatory T (Treg) cell numbers in patients with coronary artery disease. Here we combine single-cell transcriptomics and T cell receptor analyses and show that IL-2LD clonally expands effector Treg cells in patients with acute coronary syndromes. The clonally expanded Treg cells upregulate key immunosuppressive and metabolic pathways and show an increased number of predicted ligand-receptor interactions. These Treg cells also display similar predicted antigen specificities, which cluster with published sequences specific to atherosclerotic cardiovascular disease. By tracking the T cell receptors of single cells over time, we identify an inflammatory polarization of the T cell compartment after myocardial infarction, which is restrained by IL-2LD. We identify BACH2 as a repressor of the Treg effector program. However, BACH2-mediated regulation is bypassed with IL-2LD. Overall, these results lend insight into the IL-2-driven clonal expansion program in human Treg cells, with important therapeutic implications for patients with cardiovascular and other immune-mediated diseases.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217735","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

Insights from the LILACS trial on translational T cell regulation in cardiology. 从LILACS试验的见解翻译T细胞调节在心脏病学。

IF 9.4

Nature cardiovascular research Pub Date : 2025-06-03 DOI: 10.1038/s44161-025-00658-6

DiyaaElDin Ashour, Gustavo Ramos

引用次数: 0

Restraining emergency hematopoiesis preserves cardiac function after infarction. 抑制急诊造血可保护心肌梗死后的心脏功能。

IF 9.4

Nature cardiovascular research Pub Date : 2025-06-02 DOI: 10.1038/s44161-025-00675-5

Andrea Tavosanis

引用次数: 0

Angiopoietin-TIE2 feedforward circuit promotes PIK3CA-driven venous malformations. 血管生成素- tie2前馈电路促进pik3ca驱动的静脉畸形。

IF 9.4

Nature cardiovascular research Pub Date : 2025-05-23 DOI: 10.1038/s44161-025-00655-9

Marle Kraft, Hans Schoofs, Milena Petkova, Jorge Andrade, Ana Rita Grosso, Rui Benedito, An-Katrien De Roo, Laurence M Boon, Miikka Vikkula, Friedrich G Kapp, René Hägerling, Michael Potente, Taija Mäkinen

{"title":"Angiopoietin-TIE2 feedforward circuit promotes PIK3CA-driven venous malformations.","authors":"Marle Kraft, Hans Schoofs, Milena Petkova, Jorge Andrade, Ana Rita Grosso, Rui Benedito, An-Katrien De Roo, Laurence M Boon, Miikka Vikkula, Friedrich G Kapp, René Hägerling, Michael Potente, Taija Mäkinen","doi":"10.1038/s44161-025-00655-9","DOIUrl":"https://doi.org/10.1038/s44161-025-00655-9","url":null,"abstract":"Venous malformations (VMs) are vascular anomalies lacking curative treatments, often caused by somatic PIK3CA mutations that hyperactivate the PI3Kα-AKT-mTOR signaling pathway. Here, we identify a venous-specific signaling circuit driving disease progression, where excessive PI3Kα activity amplifies upstream TIE2 receptor signaling through autocrine and paracrine mechanisms. In Pik3caH1047R-driven VM mouse models, single-cell transcriptomics and lineage tracking revealed clonal expansion of mutant endothelial cells with a post-capillary venous phenotype, characterized by suppression of the AKT-inhibited FOXO1 and its target genes, including the TIE2 antagonist ANGPT2. An imbalance in TIE2 ligands, likely exacerbated by aberrant recruitment of smooth muscle cells producing the agonist ANGPT1, increased TIE2 activity in both mouse and human VMs. While mTOR blockade had limited effects on advanced VMs in mice, inhibiting TIE2 or ANGPT effectively suppressed their growth. These findings uncover a PI3K-FOXO1-ANGPT-TIE2 circuit as a core driver of PIK3CA-related VMs and highlight TIE2 as a promising therapeutic target.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133375","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

Receptor activation via phase separation affects cardiac preservation quality. 通过相分离激活受体影响心脏保存质量。

IF 9.4

Nature cardiovascular research Pub Date : 2025-05-21 DOI: 10.1038/s44161-025-00668-4

引用次数: 0

Mineralocorticoid receptor phase separation modulates cardiac preservation. 矿化皮质激素受体相分离调节心脏保存。

IF 9.4

Nature cardiovascular research Pub Date : 2025-05-19 DOI: 10.1038/s44161-025-00653-x

Ienglam Lei, Hüseyin Sicim, Wenbin Gao, Wei Huang, Pierre Emmanuel Noly, Melissa R Pergande, Mallory C Wilson, Aurora Lee, Liu Liu, Ashraf Abou El Ela, Mulan Jiang, Sahar A Saddoughi, Jordan S Pober, Jeffrey L Platt, Marilia Cascalho, Francis D Pagani, Y Eugene Chen, Bertram Pitt, Zhong Wang, Richard M Mortensen, Ying Ge, Paul C Tang

{"title":"Mineralocorticoid receptor phase separation modulates cardiac preservation.","authors":"Ienglam Lei, Hüseyin Sicim, Wenbin Gao, Wei Huang, Pierre Emmanuel Noly, Melissa R Pergande, Mallory C Wilson, Aurora Lee, Liu Liu, Ashraf Abou El Ela, Mulan Jiang, Sahar A Saddoughi, Jordan S Pober, Jeffrey L Platt, Marilia Cascalho, Francis D Pagani, Y Eugene Chen, Bertram Pitt, Zhong Wang, Richard M Mortensen, Ying Ge, Paul C Tang","doi":"10.1038/s44161-025-00653-x","DOIUrl":"10.1038/s44161-025-00653-x","url":null,"abstract":"Heart transplantation is the gold standard treatment for patients with end-stage heart failure. However, there is a shortage of donor hearts available. The short tolerable cold ischemic time for delivering donor hearts to matching recipients is closely responsible for this shortage. Here we uncover the phenomenon of mineralocorticoid receptor (MR) phase separation, which exacerbates injury to the murine and human donor heart during cold storage and can be modulated with pharmacological inhibition to improve preservation quality. Interestingly, donor cardiomyocytes strongly expressed MR, which undergoes preservation-related phase separation. The phenomenon of macromolecular phase separation is not limited to the heart or MR during preservation. Cold preservation of the lung, liver and kidney also displays phase separation of other transcriptional regulators including histone deacetylase 1 (HDAC1), bromodomain-containing 4 (BRD4) and MR. Our results reveal an understudied area of preservation biology that may be further exploited to improve the preservation of multiple solid organs.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103299","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

Left atrial wall shear stress correlates with fibrosis in patients with atrial fibrillation. 心房颤动患者左心房壁剪应力与纤维化相关。

IF 9.4

Nature cardiovascular research Pub Date : 2025-05-13 DOI: 10.1038/s44161-025-00651-z

Dionysios Adamopoulos, Georgios Rovas, Nicolas Johner, Hajo Müller, Jean-François Deux, Lindsey A Crowe, Jean-Paul Vallée, François Mach, Nikolaos Stergiopulos, Dipen Shah

{"title":"Left atrial wall shear stress correlates with fibrosis in patients with atrial fibrillation.","authors":"Dionysios Adamopoulos, Georgios Rovas, Nicolas Johner, Hajo Müller, Jean-François Deux, Lindsey A Crowe, Jean-Paul Vallée, François Mach, Nikolaos Stergiopulos, Dipen Shah","doi":"10.1038/s44161-025-00651-z","DOIUrl":"https://doi.org/10.1038/s44161-025-00651-z","url":null,"abstract":"Left atrial wall fibrosis has an important role in atrial fibrillation (AF) because of the abnormal electrophysiological properties of the fibrotic areas. However, the mechanisms behind the development of left atrial fibrosis are not well understood. Here, we examine the association between regional wall shear stress and areas with fibrosis in the left atrium of patients with AF. We recruited 15 patients with AF for an observational prospective study involving baseline three-dimensional (3D) electroanatomical mapping of the left atrium and preinterventional cardiovascular magnetic resonance imaging to detect left atrial fibrosis. We extracted a 3D anatomical model of the left atrium from the electroanatomical maps. Then, we calculated regional time-averaged wall shear stress (TAWSS) and blood stagnation by performing patient-specific computational fluid dynamic simulations. We found that fibrosis and electrical scarring were more prevalent in areas exposed to high TAWSS without blood stagnation, whereas areas with low TAWSS were associated with blood stagnation.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044422","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

Multiscale and recursive unmixing of spatiotemporal rhythms for live-cell and intravital cardiac microscopy. 活细胞和活体心脏显微镜的时空节律的多尺度和递归解混。

IF 9.4

Nature cardiovascular research Pub Date : 2025-05-01 Epub Date: 2025-05-07 DOI: 10.1038/s44161-025-00649-7

Zhi Ling, Wenhao Liu, Kyungduck Yoon, Jessica Hou, Parvin Forghani, Xuanwen Hua, Hansol Yoon, Maryam Bagheri, Lakshmi P Dasi, Biagio Mandracchia, Chunhui Xu, Shuyi Nie, Shu Jia

{"title":"Multiscale and recursive unmixing of spatiotemporal rhythms for live-cell and intravital cardiac microscopy.","authors":"Zhi Ling, Wenhao Liu, Kyungduck Yoon, Jessica Hou, Parvin Forghani, Xuanwen Hua, Hansol Yoon, Maryam Bagheri, Lakshmi P Dasi, Biagio Mandracchia, Chunhui Xu, Shuyi Nie, Shu Jia","doi":"10.1038/s44161-025-00649-7","DOIUrl":"10.1038/s44161-025-00649-7","url":null,"abstract":"Cardiovascular diseases remain a pressing public health issue, necessitating the development of advanced therapeutic strategies underpinned by precise cardiac observations. While fluorescence microscopy is an invaluable tool for probing biological processes, cardiovascular signals are often complicated by persistent autofluorescence, overlaying dynamic cardiovascular entities and nonspecific labeling from tissue microenvironments. Here we present multiscale recursive decomposition for the precise extraction of dynamic cardiovascular signals. Multiscale recursive decomposition constructs a comprehensive framework for cardiac microscopy that includes pixel-wise image enhancement, robust principal component analysis and recursive motion segmentation. This method has been validated in various cardiac systems, including in vitro studies with human induced pluripotent stem cell-derived cardiomyocytes and in vivo studies of cardiovascular morphology and function in Xenopus embryos. The approach advances light-field cardiac microscopy, facilitating simultaneous, multiparametric and volumetric analysis of cardiac activities with minimum photodamage. We anticipate that the methodology will advance cardiovascular studies across a broad spectrum of cardiac models.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":"637-648"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994074","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

Lymphatic mysteries unzipped. 淋巴的奥秘解开了。

IF 9.4

Nature cardiovascular research Pub Date : 2025-05-01 DOI: 10.1038/s44161-025-00643-z

Tatiana V Petrova, Gwendalyn J Randolph

引用次数: 0

Single-cell spatial transcriptomics of tertiary lymphoid organ-like structures in human atherosclerotic plaques. 人类动脉粥样硬化斑块中三级淋巴样器官样结构的单细胞空间转录组学。

IF 9.4

Nature cardiovascular research Pub Date : 2025-05-01 Epub Date: 2025-04-28 DOI: 10.1038/s44161-025-00639-9

Zhichao Lai, Deqiang Kong, Qingsong Li, Yue Wang, Kang Li, Xiaohan Duan, Jiang Shao, Yiyun Xie, Junye Chen, Tianjing Zhang, Yuyao Feng, Haohao Deng, Jiaxian Wang, Chaonan Wang, Keqiang Shu, Hongmei Zhao, Hanze Du, Congwei Jia, Huanyu Dai, Lizhi Xie, Jianlin Liu, Xujiao Luo, Lin Wang, Leyin Xu, Zhan Zhu, Xiangling Lei, Yuru Wang, Yixuan Yang, Yanan Liu, Yuyu Liang, Yang Yang, Jun Xie, Bao Liu, Ziqing Deng, Xin Liu

{"title":"Single-cell spatial transcriptomics of tertiary lymphoid organ-like structures in human atherosclerotic plaques.","authors":"Zhichao Lai, Deqiang Kong, Qingsong Li, Yue Wang, Kang Li, Xiaohan Duan, Jiang Shao, Yiyun Xie, Junye Chen, Tianjing Zhang, Yuyao Feng, Haohao Deng, Jiaxian Wang, Chaonan Wang, Keqiang Shu, Hongmei Zhao, Hanze Du, Congwei Jia, Huanyu Dai, Lizhi Xie, Jianlin Liu, Xujiao Luo, Lin Wang, Leyin Xu, Zhan Zhu, Xiangling Lei, Yuru Wang, Yixuan Yang, Yanan Liu, Yuyu Liang, Yang Yang, Jun Xie, Bao Liu, Ziqing Deng, Xin Liu","doi":"10.1038/s44161-025-00639-9","DOIUrl":"10.1038/s44161-025-00639-9","url":null,"abstract":"Tertiary lymphoid organs have been identified in the arterial adventitia in both mouse models of atherosclerosis and patients with atherosclerosis, yet their role in the disease remains insufficiently explored. Here we present a spatially resolved single-cell transcriptome atlas of human atherosclerotic plaques, identifying 14 distinct cell types and providing evidence of plaque tertiary lymphoid organs (PTLOs). The development of PTLOs was associated with the expression of lymphangiogenic chemokine genes and the adhesion molecule gene in fibroblast-like smooth muscle cells. PTLOs harbor abundant B cells with expanded and diversified B cell receptors, suggesting substantial immune involvement. We also observed that B cells may be exchanged between PTLOs and perivascular adipose tissues. The presence of PTLO-like structures correlates with cerebrovascular events, which may be mediated by PTLO-derived IgG antibodies enhancing macrophage functional activity. Our findings suggest the existence and characteristics of PTLOs in human atherosclerosis, elucidating their cellular functions and clinical implications and offering avenues for understanding, diagnosing and treating this condition.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":"547-566"},"PeriodicalIF":9.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060123","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