Nature cardiovascular research最新文献_第2页

Correlative imaging integrates electrophysiology with three-dimensional murine heart reconstruction to reveal electrical coupling between cell types. 相关成像将电生理学与三维小鼠心脏重建相结合，揭示细胞类型之间的电耦合。

IF 10.8

Nature cardiovascular research Pub Date : 2025-10-06 DOI: 10.1038/s44161-025-00728-9

Francesco Giardini, Camilla Olianti, Gerard A Marchal, Fernando Campos, Valentina Romanelli, Joshua Steyer, Josef Madl, Roberto Piersanti, Giulia Arecchi, Induja Perumal Vanaja, Valentina Biasci, Eva A Rog-Zielinska, Gabriella Nesi, Leslie M Loew, Elisabetta Cerbai, Stephen P Chelko, Francesco Regazzoni, Axel Loewe, Martin J Bishop, Marco Mongillo, Peter Kohl, Tania Zaglia, Callum M Zgierski-Johnston, Leonardo Sacconi

{"title":"Correlative imaging integrates electrophysiology with three-dimensional murine heart reconstruction to reveal electrical coupling between cell types.","authors":"Francesco Giardini, Camilla Olianti, Gerard A Marchal, Fernando Campos, Valentina Romanelli, Joshua Steyer, Josef Madl, Roberto Piersanti, Giulia Arecchi, Induja Perumal Vanaja, Valentina Biasci, Eva A Rog-Zielinska, Gabriella Nesi, Leslie M Loew, Elisabetta Cerbai, Stephen P Chelko, Francesco Regazzoni, Axel Loewe, Martin J Bishop, Marco Mongillo, Peter Kohl, Tania Zaglia, Callum M Zgierski-Johnston, Leonardo Sacconi","doi":"10.1038/s44161-025-00728-9","DOIUrl":"10.1038/s44161-025-00728-9","url":null,"abstract":"Cardiac fibrosis contributes to electrical conduction disturbances, yet its specific impact on conduction remains unclear, hindering predictive insight into cardiac electrophysiology and arrhythmogenesis. Arrhythmogenic cardiomyopathy is associated with fibrotic remodeling, and it accounts for most cases of stress-related arrhythmic sudden death. Here we develop a correlative imaging approach to integrate macroscale cardiac electrophysiology with three-dimensional microscale reconstructions of the ventricles. We apply this tool to a desmoglein-2 mutant mouse model to characterize the dynamics of conduction wavefronts and relate them to the underlying structural substrate. We observed that conduction through fibrotic tissue areas shows a frequency-dependent behavior, where conduction fails at high stimulation frequencies; this promotes reentrant arrhythmias, even in regions that were electrophysiologically inconspicuous at lower stimulation rates. We found that fibrotic areas undergo electrophysiological remodeling that acts as a low-pass filter for conduction, quantitatively explained by computational models informed by structural data. Collectively, our study provides a structure-function mapping pipeline and describes a pro-arrhythmogenic mechanism in arrhythmogenic cardiomyopathy.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240523","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

Spatial multiomics of acute myocardial infarction reveals immune cell infiltration through the endocardium 急性心肌梗死的空间多组学揭示免疫细胞通过心内膜浸润。

IF 10.8

Nature cardiovascular research Pub Date : 2025-10-03 DOI: 10.1038/s44161-025-00717-y

Florian Wünnemann, Florian Sicklinger, Kresimir Bestak, Jose Nimo, Tobias Thiemann, Junedh M. Amrute, Mathias Nordbeck, Niklas Hartmann, Miguel A. Ibarra-Arellano, Jovan Tanevski, Margot Chazotte, Clara Heine, Norbert Frey, Kory J. Lavine, Fabian Coscia, Julio Saez-Rodriguez, Florian Leuschner, Denis Schapiro

{"title":"Spatial multiomics of acute myocardial infarction reveals immune cell infiltration through the endocardium","authors":"Florian Wünnemann, Florian Sicklinger, Kresimir Bestak, Jose Nimo, Tobias Thiemann, Junedh M. Amrute, Mathias Nordbeck, Niklas Hartmann, Miguel A. Ibarra-Arellano, Jovan Tanevski, Margot Chazotte, Clara Heine, Norbert Frey, Kory J. Lavine, Fabian Coscia, Julio Saez-Rodriguez, Florian Leuschner, Denis Schapiro","doi":"10.1038/s44161-025-00717-y","DOIUrl":"10.1038/s44161-025-00717-y","url":null,"abstract":"Myocardial infarction (MI) continues to be a leading cause of death worldwide. Even though it is well established that the complex interplay between different cell types determines the overall healing response after MI, the precise changes in the tissue architecture are still poorly understood. In this study, we generated an integrative cellular map of the acute phase after murine MI using a combination of imaging-based transcriptomics (Molecular Cartography) and antibody-based highly multiplexed imaging (Sequential Immunofluorescence). This enabled us to evaluate cell type compositions and changes at subcellular resolution over time. We observed the recruitment of leukocytes to the infarcted heart through the endocardium and performed unbiased spatial proteomic analysis using Deep Visual Proteomics (DVP) to investigate the underlying mechanisms. DVP identified von Willebrand factor (vWF) as an upregulated mediator of inflammation 24 hours after MI, and functional blocking of vWF reduced the infiltration of C-C chemokine receptor 2 (Ccr2)-positive monocytes and worsened cardiac function after MI. Wünnemann et al. generate a subcellular resolution spatial map of the murine heart after myocardial infarction, revealing that immune cells can infiltrate the organ through the endocardium.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 10","pages":"1345-1362"},"PeriodicalIF":10.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-025-00717-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226306","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

Oxidative phosphorylation is required for fish heart regeneration 氧化磷酸化是鱼心脏再生所必需的。

IF 10.8

Nature cardiovascular research Pub Date : 2025-10-02 DOI: 10.1038/s44161-025-00723-0

引用次数: 0

Vutrisiran improves cardiac structure and function in individuals with transthyretin amyloidosis with cardiomyopathy Vutrisiran改善甲状腺转蛋白淀粉样变合并心肌病患者的心脏结构和功能。

IF 10.8

Nature cardiovascular research Pub Date : 2025-10-02 DOI: 10.1038/s44161-025-00736-9

Gerburg Schwaerzer

引用次数: 0

ANTXR1 blockade enhances cardiac function in preclinical models of heart failure. ANTXR1阻断可增强心衰临床前模型的心功能。

IF 10.8

Nature cardiovascular research Pub Date : 2025-10-02 DOI: 10.1038/s44161-025-00725-y

Nicola Boccella, GuoJun Yu, Steven Seaman, Yang Feng, Jaewon Lee, Francesco Tomassoni-Ardori, Liping Yang, Kuo-Sheng Hsu, James M Dunleavey, Jodi Becker, Mary Beth Hilton, Karen Morris, Niza Borchin, Daeho So, Pradip Bajgain, Sudhirkumar Yanpallewar, Ryan T Gross, Krish C Dewan, Dawn E Bowles, Darren A Yuen, Lino Tessarollo, Brad St Croix

{"title":"ANTXR1 blockade enhances cardiac function in preclinical models of heart failure.","authors":"Nicola Boccella, GuoJun Yu, Steven Seaman, Yang Feng, Jaewon Lee, Francesco Tomassoni-Ardori, Liping Yang, Kuo-Sheng Hsu, James M Dunleavey, Jodi Becker, Mary Beth Hilton, Karen Morris, Niza Borchin, Daeho So, Pradip Bajgain, Sudhirkumar Yanpallewar, Ryan T Gross, Krish C Dewan, Dawn E Bowles, Darren A Yuen, Lino Tessarollo, Brad St Croix","doi":"10.1038/s44161-025-00725-y","DOIUrl":"https://doi.org/10.1038/s44161-025-00725-y","url":null,"abstract":"Heart disease, a leading cause of mortality worldwide, is in urgent need of improved therapies. Fibrosis, an accumulation of collagen-rich extracellular matrix in response to injury, is a hallmark of heart disease, but clinical agents that can interfere with the fibrotic pathway do not yet exist. Here we show that ANTXR1/TEM8, a pathology-induced transmembrane protein required for collagen removal, exacerbates injury in multiple models of heart failure. Genetic disruption of Antxr1 and treatment with human neutralizing antibodies prevented heart deterioration following acute myocardial infarction. ANTXR1 pharmacological blockade also improved heart function in models of pressure overload and obesity-induced heart disease with preserved ejection fraction. Improved heart function was accompanied by enhanced exercise tolerance. Mechanistic studies revealed an ANTXR1-antibody-driven improvement in post-infarct scar formation followed by attenuation of late-stage, chronic TGFβ-mediated extracellular matrix remodeling. Thus, ANTXR1-mediated collagen turnover during heart failure is both maladaptive and druggable, providing avenues for therapeutic intervention.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214631","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

Oxidative phosphorylation is required for cardiomyocyte re-differentiation and long-term fish heart regeneration 氧化磷酸化是心肌细胞再分化和长期心脏再生所必需的。

IF 10.8

Nature cardiovascular research Pub Date : 2025-10-01 DOI: 10.1038/s44161-025-00718-x

Konstantinos Lekkos, Zhilian Hu, Phong D. Nguyen, Hessel Honkoop, Esra Sengul, Rita Alonaizan, Jana Koth, Jun Ying, Madeleine E. Lemieux, Alisha Kenward, Sean Keeley, Bastiaan Spanjaard, Brett W. C. Kennedy, Xin Sun, Katherine Banecki, Helen G. Potts, Gennaro Ruggiero, James Montgomery, Daniela Panáková, Jan Philipp Junker, Lisa C. Heather, Xiaonan Wang, Juan Manuel Gonzalez-Rosa, Jeroen Bakkers, Mathilda T. M. Mommersteeg

{"title":"Oxidative phosphorylation is required for cardiomyocyte re-differentiation and long-term fish heart regeneration","authors":"Konstantinos Lekkos, Zhilian Hu, Phong D. Nguyen, Hessel Honkoop, Esra Sengul, Rita Alonaizan, Jana Koth, Jun Ying, Madeleine E. Lemieux, Alisha Kenward, Sean Keeley, Bastiaan Spanjaard, Brett W. C. Kennedy, Xin Sun, Katherine Banecki, Helen G. Potts, Gennaro Ruggiero, James Montgomery, Daniela Panáková, Jan Philipp Junker, Lisa C. Heather, Xiaonan Wang, Juan Manuel Gonzalez-Rosa, Jeroen Bakkers, Mathilda T. M. Mommersteeg","doi":"10.1038/s44161-025-00718-x","DOIUrl":"10.1038/s44161-025-00718-x","url":null,"abstract":"In contrast to humans, fish can fully regenerate their hearts after cardiac injury. However, not all fish have the same regenerative potential, allowing comparative inter-species and intra-species analysis to identify the mechanisms controlling successful heart regeneration. Here we report a differential regenerative response to cardiac cryo-injury among different wild-type zebrafish strains. Correlating these data with single-cell and bulk RNA sequencing data, we identify oxidative phosphorylation (OXPHOS) as a positive regulator of long-term regenerative outcome. OXPHOS levels, driven by glycolysis through the malate-aspartate shuttle, increase as soon as cardiomyocyte proliferation decreases, and this increase is required for cardiomyocyte re-differentiation and successful long-term regeneration. Reduced upregulation of OXPHOS in Astyanax mexicanus cavefish results in the absence of a dynamic temporal sarcomere gene expression program during cardiomyocyte re-differentiation. These findings challenge the assumption that OXPHOS inhibits regeneration and reveal targetable pathways to enhance heart repair in humans after myocardial infarction. Lekkos et al. show that a metabolic switch toward oxidative phosphorylation is required for cardiomyocyte re-differentiation and heart regeneration after injury in fish.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 10","pages":"1363-1380"},"PeriodicalIF":10.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-025-00718-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208348","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

Targeted glycophagy ATG8 therapy reverses diabetic heart disease in mice and in human engineered cardiac tissues. 靶向糖吞噬ATG8治疗在小鼠和人类工程心脏组织中逆转糖尿病性心脏病。

IF 10.8

Nature cardiovascular research Pub Date : 2025-09-29 DOI: 10.1038/s44161-025-00726-x

K M Mellor, U Varma, P Koutsifeli, C L Curl, J V Janssens, L J Daniels, G B Bernasochi, A J A Raaijmakers, M Annandale, X Li, S L James, D J Taylor, K Raedschelders, K L Weeks, R J Mills, R G Parton, X Hu, J R Bell, T J O'Brien, R Katare, E R Porrello, J E Hudson, R P Xiao, J E Van Eyk, R A Gottlieb, L M D Delbridge

{"title":"Targeted glycophagy ATG8 therapy reverses diabetic heart disease in mice and in human engineered cardiac tissues.","authors":"K M Mellor, U Varma, P Koutsifeli, C L Curl, J V Janssens, L J Daniels, G B Bernasochi, A J A Raaijmakers, M Annandale, X Li, S L James, D J Taylor, K Raedschelders, K L Weeks, R J Mills, R G Parton, X Hu, J R Bell, T J O'Brien, R Katare, E R Porrello, J E Hudson, R P Xiao, J E Van Eyk, R A Gottlieb, L M D Delbridge","doi":"10.1038/s44161-025-00726-x","DOIUrl":"10.1038/s44161-025-00726-x","url":null,"abstract":"Diabetic heart disease is highly prevalent and is associated with the early development of impaired diastolic relaxation. The mechanisms of diabetic heart disease are poorly understood, and it is a condition for which there are no targeted therapies. Recently, disrupted glycogen autophagy (glycophagy) and glycogen accumulation have been identified in the diabetic heart. Glycophagy involves glycogen receptor binding and linking with an ATG8 protein to locate and degrade glycogen within an intracellular phagolysosome. Here we show that glycogen receptor protein starch binding domain protein 1 (STBD1) is mobilized early in the cardiac glycogen response to metabolic challenge in vivo, and that deficiency of a specific ATG8 family protein, γ-aminobutyric acid type A receptor-associated protein-like 1 (GABARAPL1), is associated with diastolic dysfunction in diabetes. Gabarapl1 gene delivery treatment remediated cardiomyocyte and cardiac diastolic dysfunction in type 2 diabetic mice and the diastolic performance of 'diabetic' human induced pluripotent stem cell-derived cardiac organoids. We identify glycophagy dysregulation as a mechanism and potential treatment target for diabetic heart disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194142","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

Association of air pollution exposure and genetic susceptibility with increased risk of thoracic aortic aneurysm and dissection 空气污染暴露和遗传易感性与胸主动脉瘤和夹层风险增加的关系。

IF 10.8

Nature cardiovascular research Pub Date : 2025-09-26 DOI: 10.1038/s44161-025-00719-w

Yudiyang Ma, Jianing Wang, Linxi Tang, Feipeng Cui, Lei Zheng, Meiqi Xing, Yaohua Tian

{"title":"Association of air pollution exposure and genetic susceptibility with increased risk of thoracic aortic aneurysm and dissection","authors":"Yudiyang Ma, Jianing Wang, Linxi Tang, Feipeng Cui, Lei Zheng, Meiqi Xing, Yaohua Tian","doi":"10.1038/s44161-025-00719-w","DOIUrl":"10.1038/s44161-025-00719-w","url":null,"abstract":"Thoracic aortic aneurysm and dissection (TAAD) represent a serious health threat, yet the role of air pollution exposure on its development has been underexplored. Here we investigate the relationships between air pollutants and TAAD incidence. In a Cox’s proportional hazards model, hazard ratios (95% confidence intervals) of TAAD for an interquartile range increase in air pollutants were 2.15 (1.96, 2.35) for particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5; per 2.15 μg m−3 increase), 1.76 (1.61, 1.92) for PM10 (per 2.99 μg m−3 increase), 1.45 (1.34, 1.58) for NO2 (per 6.97 μg m−3 increase) and 1.40 (1.29, 1.51) for NOx (per 11.58 μg m−3 increase). These estimates remained consistent when using inverse probability weighting and generalized propensity score methods. Furthermore, this study revealed potential joint effects and interactions between air pollutants and genetic susceptibility on TAAD risk, especially the multiplicative and additive interactions between PM2.5 and genetic susceptibility. Air pollution exposure is associated with an increased TAAD risk and genetic susceptibility modifies this association. Ma et al. demonstrate that air pollution is associated with an increased risk of thoracic aortic aneurysm and dissection (TAAD), and that genetic susceptibility to TAAD amplifies this risk through multiplicative and additive interactions.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 10","pages":"1397-1408"},"PeriodicalIF":10.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180705","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

Interaction of PGC-1α and GDF15 in the stressed heart 应激心脏中PGC-1α和GDF15的相互作用。

IF 10.8

Nature cardiovascular research Pub Date : 2025-09-26 DOI: 10.1038/s44161-025-00729-8

Rong Tian

引用次数: 0

Author Correction: Human ocular fluid outflow on-chip reveals trabecular meshwork-mediated Schlemm’s canal endothelial dysfunction in steroid-induced glaucoma 作者更正：芯片上的人眼液流出显示激素性青光眼中小梁网介导的施莱姆管内皮功能障碍。

IF 10.8

Nature cardiovascular research Pub Date : 2025-09-26 DOI: 10.1038/s44161-025-00730-1

Renhao Lu, Anna M. Kolarzyk, W. Daniel Stamer, Esak Lee

引用次数: 0