Nature cardiovascular research最新文献

{"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}

{"title":"Receptor activation via phase separation affects cardiac preservation quality","authors":"","doi":"10.1038/s44161-025-00668-4","DOIUrl":"10.1038/s44161-025-00668-4","url":null,"abstract":"A phenomenon of mineralocorticoid receptor phase separation exacerbates injury to mouse and human donor hearts during cold storage. Pharmacological inhibition of the mineralocorticoid receptor reduces the phase separation potential and improves preservation quality.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 6","pages":"659-660"},"PeriodicalIF":10.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121603","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":"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. Lei et al. show that cold preservation of heart transplants triggers mineralocorticoid receptor clustering in cardiomyocyte nuclei, and blocking this improves heart transplant function.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 6","pages":"710-726"},"PeriodicalIF":10.8,"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}

{"title":"Signal tunnels of the developing heart","authors":"Vesna Todorovic","doi":"10.1038/s44161-025-00667-5","DOIUrl":"10.1038/s44161-025-00667-5","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 5","pages":"499-499"},"PeriodicalIF":10.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087081","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":"Developing cardiac digital twin populations powered by machine learning provides electrophysiological insights in conduction and repolarization","authors":"Shuang Qian, Devran Ugurlu, Elliot Fairweather, Laura Dal Toso, Yu Deng, Marina Strocchi, Ludovica Cicci, Richard E. Jones, Hassan Zaidi, Sanjay Prasad, Brian P. Halliday, Daniel Hammersley, Xingchi Liu, Gernot Plank, Edward Vigmond, Reza Razavi, Alistair Young, Pablo Lamata, Martin Bishop, Steven Niederer","doi":"10.1038/s44161-025-00650-0","DOIUrl":"10.1038/s44161-025-00650-0","url":null,"abstract":"Large-cohort imaging and diagnostic studies often assess cardiac function but overlook underlying biological mechanisms. Cardiac digital twins (CDTs) are personalized physics-constrained and physiology-constrained in silico representations, uncovering multi-scale insights tied to these mechanisms. In this study, we constructed 3,461 CDTs from the UK Biobank and another 359 from an ischemic heart disease (IHD) cohort, using cardiac magnetic resonance images and electrocardiograms. We show here that sex-specific differences in QRS duration were fully explained by myocardial anatomy while their myocardial conduction velocity (CV) remains similar across sexes but changes with age and obesity, indicating myocardial tissue remodeling. Longer QTc intervals in obese females were attributed to larger delayed rectifier potassium conductance $${G}_{rm{KrKs}}$$ . These findings were validated in the IHD cohort. Moreover, CV and $${G}_{rm{KrKs}}$$ were associated with cardiac function, lifestyle and mental health phenotypes, and CV was also linked with adverse clinical outcomes. Our study demonstrates how CDT development at scale reveals biological insights across populations. Qian et al. used cardiac magnetic resonance images and electrocardiograms from the UK Biobank and an ischemic heart disease cohort and developed more than 3,500 cardiac digital twins. They demonstrate that the myocardial anatomy causes differences in the QRS duration among sexes while age and body weight alter potassium conductance and myocardial conduction velocity.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 5","pages":"624-636"},"PeriodicalIF":10.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087079","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":"Cardiovascular imaging techniques for electrophysiologists","authors":"Albert J. Rogers, Olga Reynbakh, Adnan Ahmed, Mina K. Chung, Rishi Charate, Hirad Yarmohammadi, Rakesh Gopinathannair, Hassan Khan, Dhanunjaya Lakkireddy, Miguel Leal, Uma Srivatsa, Natalia Trayanova, Elaine Y. Wan","doi":"10.1038/s44161-025-00648-8","DOIUrl":"10.1038/s44161-025-00648-8","url":null,"abstract":"Rapid technological advancements in noninvasive and invasive imaging including echocardiography, computed tomography, magnetic resonance imaging and positron emission tomography have allowed for improved anatomical visualization and precise measurement of cardiac structure and function. These imaging modalities allow for evaluation of how cardiac substrate changes, such as myocardial wall thickness, fibrosis, scarring and chamber enlargement and/or dilation, have an important role in arrhythmia initiation and perpetuation. Here, we review the various imaging techniques and modalities used by clinical and basic electrophysiologists to study cardiac arrhythmia mechanisms, periprocedural planning, risk stratification and precise delivery of ablation therapy. We also review the use of artificial intelligence and machine learning to improve identification of areas for triggered activity and isthmuses in reentrant arrhythmias, which may be favorable ablation targets. Rogers et al. review the current imaging modalities to investigate the mechanisms of cardiac arrhythmias and discuss the future impact of machine learning and artificial intelligence on digital imaging.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 5","pages":"514-525"},"PeriodicalIF":10.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025896","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":"Metabolome-wide association identifies ferredoxin-1 (FDX1) as a determinant of cholesterol metabolism and cardiovascular risk in Asian populations","authors":"Nilanjana Sadhu, Rinkoo Dalan, Pritesh R. Jain, Chang Jie Mick Lee, Leroy Sivappiragasam Pakkiri, Kai Yi Tay, Theresia H. Mina, Dorrain Low, Yilin Min, Matthew Ackers-Johnson, Thi Tun Thi, Vishnu Goutham Kota, Yu Shi, Yan Liu, Hanry Yu, Vicky Lai, Yang Yang, Darwin Tay, Hong Kiat Ng, Xiaoyan Wang, Kari E. Wong, Max Lam, Xue Li Guan, Nicolas Bertin, Eleanor Wong, James Best, Rangaprasad Sarangarajan, Paul Elliott, Elio Riboli, Jimmy Lee, Eng Sing Lee, Joanne Ngeow, Patrick Tan, Christine Cheung, Chester Lee Drum, Roger SY Foo, Gregory A. Michelotti, Haojie Yu, Patricia A. Sheridan, Marie Loh, John C. Chambers","doi":"10.1038/s44161-025-00638-w","DOIUrl":"10.1038/s44161-025-00638-w","url":null,"abstract":"The burden of cardiovascular disease is rising in the Asia-Pacific region, in contrast to falling cardiovascular disease mortality rates in Europe and North America. Here we perform quantification of 883 metabolites by untargeted mass spectroscopy in 8,124 Asian adults and investigate their relationships with carotid intima media thickness, a marker of atherosclerosis. Plasma concentrations of 3beta-hydroxy-5-cholestenoate (3BH5C), a cholesterol metabolite, were inversely associated with carotid intima media thickness, and Mendelian randomization studies supported a causal relationship between 3BH5C and coronary artery disease. The observed effect size was 5- to 6-fold higher in Asians than Europeans. Colocalization analyses indicated the presence of a shared causal variant between 3BH5C plasma levels and messenger RNA and protein expression of ferredoxin-1 (FDX1), a protein that is essential for sterol and bile acid synthesis. We validated FDX1 as a regulator of 3BH5C synthesis in hepatocytes and macrophages and demonstrated its role in cholesterol efflux in macrophages and aortic smooth muscle cells, using knockout and overexpression models. Sadhu et al. identify and functionally validate ferredoxin-1 (FDX1) as a determinant of cholesterol metabolism and cardiovascular risk in Asian populations.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 5","pages":"567-583"},"PeriodicalIF":10.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060543","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 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":"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. Adamopoulos, Rovas et al. show that high regional wall shear stress correlates with fibrosis and electrical scarring in the left atrium of patients with atrial fibrillation, providing insight into the development of fibrotic tissue.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 6","pages":"677-688"},"PeriodicalIF":10.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044422","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":"Functional genomics identifies a protective role for FDX1 in atherosclerosis","authors":"Nicole Wayne, Marie A. Guerraty","doi":"10.1038/s44161-025-00636-y","DOIUrl":"10.1038/s44161-025-00636-y","url":null,"abstract":"A multi-omics study in the Health for Life in Singapore (HELIOS) study uncovered novel associations among rs10488763, FDX1, the reverse cholesterol-transport pathway, and atheroprotection. This elegant functional genomics study illustrates the potential of integrated ‘-omics’ to uncover novel pathways and potential therapeutic targets.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 5","pages":"503-504"},"PeriodicalIF":10.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013958","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":"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. Ling, Liu and colleagues introduce MSR, a multiscale recursive algorithm that enhances cardiac microscopy for precise cardiovascular signal extraction, and validate the approach in vitro and in vivo.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 5","pages":"637-648"},"PeriodicalIF":10.8,"publicationDate":"2025-05-07","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}