Nature cardiovascular research最新文献

A tunable gene therapy for heart regeneration. 心脏再生的可调基因疗法。

IF 9.4

Nature cardiovascular research Pub Date : 2025-06-13 DOI: 10.1038/s44161-025-00666-6

Gabriele D'Uva

引用次数: 0

The drug-elicitable alternative splicing module for tunable vector expression in the heart. 用于心脏可调载体表达的药物诱导替代剪接模块。

IF 9.4

Nature cardiovascular research Pub Date : 2025-06-13 DOI: 10.1038/s44161-025-00665-7

Zhan Chen, Luzi Yang, Yueyang Zhang, Jiting Li, Yuhan Yang, Yue Li, Linwei Fan, Wei Chen, Lei Miao, Jin Liu, Gonglie Chen, Ze Wang, Yifei Li, Fei Gao, Jing Zhou, Lemin Zheng, Yan Zhang, Dongyu Zhao, William T Pu, Ke Yang, Erdan Dong, Yuxuan Guo

{"title":"The drug-elicitable alternative splicing module for tunable vector expression in the heart.","authors":"Zhan Chen, Luzi Yang, Yueyang Zhang, Jiting Li, Yuhan Yang, Yue Li, Linwei Fan, Wei Chen, Lei Miao, Jin Liu, Gonglie Chen, Ze Wang, Yifei Li, Fei Gao, Jing Zhou, Lemin Zheng, Yan Zhang, Dongyu Zhao, William T Pu, Ke Yang, Erdan Dong, Yuxuan Guo","doi":"10.1038/s44161-025-00665-7","DOIUrl":"https://doi.org/10.1038/s44161-025-00665-7","url":null,"abstract":"Adeno-associated viruses (AAVs) are commonly used for gene therapy, but a clinically relevant method to fine-tune AAV expression is lacking, restricting their therapeutic efficacy and safety. Here we develop the drug-elicitable alternative splicing module (DreAM), which is responsive to risdiplam, a Food and Drug Administration-approved alternative splicing modulator. Risdiplam activated DreAM-regulated AAV expression in a dose-dependent manner with a 2,000-fold inducible change, depending on the dose of risdiplam and the organ of interest. With a temporal resolution of 2 days, DreAM could transiently, reversibly and repeatedly activate AAV expression according to the frequency and duration of risdiplam administration. In this proof-of-concept study, we incorporated DreAM into the cardiomyocyte-specific, liver-detargeted AAV9-Tnnt2-miR122TS vector to transiently activate the cardiomyocyte regeneration factor YAP5SA. A dedifferentiation-proliferation-redifferentiation cycle was established in adult cardiomyocytes, improving cardiac regeneration after myocardial infarction while limiting animal death, AAV9-Tnnt2 expression in the liver and hepatic tumorigenesis. Therefore, DreAM may enhance the efficacy, safety and scope of gene therapy.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295455","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

Secondary analysis of the EMPACT-MI trial reveals cardiovascular-kidney efficacy and safety of empagliflozin after acute myocardial infarction. EMPACT-MI试验的二次分析揭示了急性心肌梗死后恩格列净对心血管和肾脏的疗效和安全性。

IF 9.4

Nature cardiovascular research Pub Date : 2025-06-13 DOI: 10.1038/s44161-025-00657-7

Rahul Aggarwal, Deepak L Bhatt, Adrian F Hernandez, Stefan D Anker, Josephine Harrington, W Schuyler Jones, Michaela Mattheus, Mark C Petrie, Dominik Steubl, Mikhail Sumin, Vikram Thanam, Jacob A Udell, Javed Butler

{"title":"Secondary analysis of the EMPACT-MI trial reveals cardiovascular-kidney efficacy and safety of empagliflozin after acute myocardial infarction.","authors":"Rahul Aggarwal, Deepak L Bhatt, Adrian F Hernandez, Stefan D Anker, Josephine Harrington, W Schuyler Jones, Michaela Mattheus, Mark C Petrie, Dominik Steubl, Mikhail Sumin, Vikram Thanam, Jacob A Udell, Javed Butler","doi":"10.1038/s44161-025-00657-7","DOIUrl":"https://doi.org/10.1038/s44161-025-00657-7","url":null,"abstract":"Data on the cardiovascular-kidney effects and safety of empagliflozin among patients with acute myocardial infarction are limited. EMPACT-MI (Study to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) was a double-blind, multicenter clinical trial that randomized 6,522 patients with acute myocardial infarction and risk for heart failure to empagliflozin or placebo. Here we show in this secondary analysis that the mean estimated glomerular filtration rate at baseline was 76.1 ml min-1 1.73 m-2 (s.d. = 19.9 ml min-1 1.73 m-2), with longitudinal kidney function data available for 1,152 (17.7%) treated patients from select countries. By 24 months, compared with baseline, the estimated glomerular filtration rate was similar in the empagliflozin group but declined in the placebo group (P = 0.01). Empagliflozin reduced the total adverse events of heart failure or all-cause mortality irrespective of kidney function (Pinteraction = 0.30). Thirty-day adverse event rates were similar by treatment group and consistent across baseline kidney function. Empagliflozin had kidney-protective effects, reduced heart failure outcomes and was safe to initiate soon after acute myocardial infarction across baseline kidney function.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295454","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

Reversal of cerebrovascular anomalies in a zebrafish model of vein of Galen aneurysm. 斑马鱼盖伦动脉瘤静脉模型脑血管异常的逆转。

IF 9.4

Nature cardiovascular research Pub Date : 2025-06-12 DOI: 10.1038/s44161-025-00659-5

Edwige Martin-Valiente, Yao Du, Chloé Goemans, Michelle America, Egor Zindy, Myckel Adam, Benoit Scheid, Miikka Vikkula, Boris Lubicz, Benoit Vanhollebeke, Nicolas Baeyens

{"title":"Reversal of cerebrovascular anomalies in a zebrafish model of vein of Galen aneurysm.","authors":"Edwige Martin-Valiente, Yao Du, Chloé Goemans, Michelle America, Egor Zindy, Myckel Adam, Benoit Scheid, Miikka Vikkula, Boris Lubicz, Benoit Vanhollebeke, Nicolas Baeyens","doi":"10.1038/s44161-025-00659-5","DOIUrl":"https://doi.org/10.1038/s44161-025-00659-5","url":null,"abstract":"Congenital vascular malformations result from abnormal development of the vascular tree, with the aneurysmal malformation of the vein of Galen (VGAM) being the most prevalent neurovascular malformation in neonates, associated with poor outcomes. This condition is linked to germline mutations in the RASA1 and EPHB4 genes, although the underlying developmental mechanisms remain unclear. Here we generate zebrafish models lacking rasa1a and ephb4a that replicate the genetic and structural features of VGAMs. Our findings connect the development of malformations to insufficient fusion of precursor blood vessels, a process regulated by blood flow and the responses of endothelial cells. RASA1 deficiency destabilizes the homeostatic response to blood flow and contributes to impaired flow-mediated activation of MAPK and phosphatidylinositol-3-kinase signaling. By pharmacologically targeting these signaling pathways in mutant models, we restore normal fusion in existing malformations, offering potential new strategies for treating VGAMs and similar vascular remodeling disorders.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287501","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

The sequence of changes in intravascular imaging findings during lipid-lowering therapy and its implication. 降脂治疗期间血管内影像学改变的顺序及其意义。

IF 9.4

Nature cardiovascular research Pub Date : 2025-06-11 DOI: 10.1038/s44161-025-00664-8

Daichi Fujimoto, Valentin Fuster, Ik-Kyung Jang

引用次数: 0

Pioneer factor ETV2 safeguards endothelial cell specification by recruiting the repressor REST to restrict alternative lineage commitment. 先锋因子ETV2通过招募抑制因子REST来限制替代谱系承诺，从而保护内皮细胞规格。

IF 9.4

Nature cardiovascular research Pub Date : 2025-06-10 DOI: 10.1038/s44161-025-00660-y

Danyang Chen, Xiaonuo Fan, Ninghe Sun, Kai Wang, Liyan Gong, Juan M Melero-Martin, William T Pu

{"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.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"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}

引用次数: 0

Ketogenic capacity of the heart determines the outcome of heart failure. 心脏的生酮能力决定心力衰竭的结果。

IF 9.4

Nature cardiovascular research Pub Date : 2025-06-06 DOI: 10.1038/s44161-025-00676-4

Gerburg Schwaerzer

引用次数: 0

BMAL1-HIF2A mediates diurnal cardioprotection during myocardial injury. BMAL1-HIF2A介导心肌损伤时的昼夜心脏保护。

IF 9.4

Nature cardiovascular research Pub Date : 2025-06-05 DOI: 10.1038/s44161-025-00678-2

Elisa Martinif

引用次数: 0

Epistasis in cardiac traits. 心脏性状的上位性。

IF 9.4

Nature cardiovascular research Pub Date : 2025-06-05 DOI: 10.1038/s44161-024-00595-w

Julian Stamp, Lorin Crawford

引用次数: 0

Epistasis regulates genetic control of cardiac hypertrophy. 上位调节心脏肥厚的遗传控制。

IF 9.4

Nature cardiovascular research Pub Date : 2025-06-05 DOI: 10.1038/s44161-025-00656-8

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

{"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.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236135","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