Nature cardiovascular research最新文献

{"title":"The sequence of changes in intravascular imaging findings during lipid-lowering therapy and its implication","authors":"Daichi Fujimoto, Valentin Fuster, Ik-Kyung Jang","doi":"10.1038/s44161-025-00664-8","DOIUrl":"10.1038/s44161-025-00664-8","url":null,"abstract":"Over the past two decades, studies with serial coronary imaging have consistently shown favorable changes in plaque phenotype in response to lipid-lowering therapy (LLT). Here, we review these studies, which had varied follow-up periods, to examine the time course of changes in plaque phenotype. The plaque response to LLT appears to start with the thickening of the fibrous cap, followed by a decrease in lipid components and ultimately a regression in plaque volume. Thickening of the fibrous cap is not only the earliest and most sensitive response to LLT but, in combination with a reduction in lipid components, provides protection from coronary artery disease. The small yet significant regression in plaque volume observed in serial studies is suggested to be more indicative of plaque stabilization than lumen expansion. The insight gained from integrating the current literature will help inform better lipid management in clinical practice and guide the design of future studies. Fujimoto et al. provide a review of studies with serial coronary imaging in patients with lipid-lowering therapy and discuss the time course of the changes in plaque composition and burden.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 6","pages":"661-676"},"PeriodicalIF":10.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276894","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":"Pioneer factor ETV2 safeguards endothelial cell specification by recruiting the repressor REST to restrict alternative lineage commitment","authors":"Danyang Chen, Xiaonuo Fan, Ninghe Sun, Kai Wang, Liyan Gong, Juan M. Melero-Martin, William T. Pu","doi":"10.1038/s44161-025-00660-y","DOIUrl":"10.1038/s44161-025-00660-y","url":null,"abstract":"Mechanisms of cell fate specification are central to developmental biology and regenerative medicine. ETV2 is a master regulator for the endothelial cell (EC) lineage specification. Here we study mechanisms by which ETV2 overexpression in human induced pluripotent stem-cell-derived mesodermal progenitors efficiently specifies ECs. We used CUT&RUN, scRNA-seq and scATAC-seq to characterize the molecular features of EC differentiation mediated by ETV2. We defined the scope of ETV2 pioneering activity and identified its direct downstream target genes. Induced ETV2 expression both directed specification of endothelial progenitors and suppressed acquisition of alternative fates. Functional screening and candidate validation revealed cofactors essential for efficient EC specification, including the transcriptional activator GABPA. Notably, the transcriptional repressor REST was also necessary for efficient EC specification. ETV2 recruited REST to repress non-EC lineage genes. Our study provides an unparalleled molecular analysis of EC specification at single-cell resolution and highlights the important role of pioneer factors to recruit repressors that suppress commitment to alternative lineages. Chen et al. employ multiple approaches to show that ETV2 recruits the transcriptional repressor REST, facilitating mesoderm-to-endothelial cell specification, while simultaneously preventing iPS cell-derived mesodermal stem cells from differentiating into alternative lineages.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 6","pages":"689-709"},"PeriodicalIF":10.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268006","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":"Ketogenic capacity of the heart determines the outcome of heart failure","authors":"Gerburg Schwaerzer","doi":"10.1038/s44161-025-00676-4","DOIUrl":"10.1038/s44161-025-00676-4","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 6","pages":"649-649"},"PeriodicalIF":10.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251192","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":"BMAL1–HIF2A mediates diurnal cardioprotection during myocardial injury","authors":"Elisa Martini","doi":"10.1038/s44161-025-00678-2","DOIUrl":"10.1038/s44161-025-00678-2","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 6","pages":"651-651"},"PeriodicalIF":10.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236133","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":"Epistasis in cardiac traits","authors":"Julian Stamp, Lorin Crawford","doi":"10.1038/s44161-024-00595-w","DOIUrl":"10.1038/s44161-024-00595-w","url":null,"abstract":"Finding phenotypic variance that results from gene interactions (epistasis) has been a longstanding challenge in human genetics. The combination of a new machine learning framework with functional genomics now provides evidence that cardiac hypertrophy is regulated by non-additive genetic interactions.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 6","pages":"655-656"},"PeriodicalIF":10.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236134","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":"Epistasis regulates genetic control of cardiac hypertrophy","authors":"Qianru Wang, Tiffany M. Tang, Michelle Youlton, Chad S. Weldy, Ana M. Kenney, Omer Ronen, J. Weston Hughes, Elizabeth T. Chin, Shirley C. Sutton, Abhineet Agarwal, Xiao Li, Merle Behr, Karl Kumbier, Christine S. Moravec, W. H. Wilson Tang, Kenneth B. Margulies, Thomas P. Cappola, Atul J. Butte, Rima Arnaout, James B. Brown, James R. Priest, Victoria N. Parikh, Bin Yu, Euan A. Ashley","doi":"10.1038/s44161-025-00656-8","DOIUrl":"10.1038/s44161-025-00656-8","url":null,"abstract":"Although genetic variant effects often interact nonadditively, strategies to uncover epistasis remain in their infancy. Here we develop low-signal signed iterative random forests to elucidate the complex genetic architecture of cardiac hypertrophy, using deep learning-derived left ventricular mass estimates from 29,661 UK Biobank cardiac magnetic resonance images. We report epistatic variants near CCDC141, IGF1R, TTN and TNKS, identifying loci deemed insignificant in genome-wide association studies. Functional genomic and integrative enrichment analyses reveal that genes mapped from these loci share biological process gene ontologies and myogenic regulatory factors. Transcriptomic network analyses using 313 human hearts demonstrate strong co-expression correlations among these genes in healthy hearts, with significantly reduced connectivity in failing hearts. To assess causality, RNA silencing in human induced pluripotent stem cell-derived cardiomyocytes, combined with novel microfluidic single-cell morphology analysis, confirms that cardiomyocyte hypertrophy is nonadditively modifiable by interactions between CCDC141, TTN and IGF1R. Our results expand the scope of cardiac genetic regulation to epistasis. Wang, Tang and colleagues develop the low-signal signed iterative random forest pipeline to investigate epistasis in the genetic control of cardiac hypertrophy, identifying epistatic variants near CCDC141, IGF1R, TTN and TNKS loci, and show that hypertrophy in induced pluripotent stem cell-derived cardiomyocytes is nonadditively influenced by interactions among CCDC141, TTN and IGF1R.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 6","pages":"740-760"},"PeriodicalIF":10.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236135","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":"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":"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. By integrating single-cell transcriptomics and T cell receptor repertoire analyses of regulatory T (Treg) cells in a cohort of patients with acute coronary syndrome from the LILACS trial, Case et al. show that low-dose interleukin-2 clonally expands Treg cells and maintains their suppressive program by bypassing BACH2 downregulation.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 6","pages":"727-739"},"PeriodicalIF":10.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217735","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":"Insights from the LILACS trial on translational T cell regulation in cardiology","authors":"DiyaaElDin Ashour, Gustavo Ramos","doi":"10.1038/s44161-025-00658-6","DOIUrl":"10.1038/s44161-025-00658-6","url":null,"abstract":"Immunomodulatory approaches have gained momentum in cardiology. A report now highlights how low-dose interleukin-2 treatment expands regulatory T cells, reducing inflammation, in patients with acute coronary syndrome, shedding light on T cell antigen specificity and differentiation in cardiovascular disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 6","pages":"652-654"},"PeriodicalIF":10.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217734","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":"Restraining emergency hematopoiesis preserves cardiac function after infarction","authors":"Andrea Tavosanis","doi":"10.1038/s44161-025-00675-5","DOIUrl":"10.1038/s44161-025-00675-5","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 6","pages":"650-650"},"PeriodicalIF":10.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210352","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":"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":"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. Kraft et al. identify TIE2 activation as a key driver of PIK3CA-related venous malformations and demonstrate that inhibiting TIE2 signaling can suppress the growth of advanced lesions.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 7","pages":"801-820"},"PeriodicalIF":10.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133375","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}