Nature cardiovascular research最新文献_第7页

Selective titin cleavage disrupts cardiac mechanical homeostasis to drive heart failure and fibrosis 选择性titin切割破坏心脏机械稳态，导致心力衰竭和纤维化

IF 12.6

Nature cardiovascular research Pub Date : 2026-06-16 DOI: 10.1038/s44161-026-00829-z

Johanna K. Freundt, Paulina Hartmann, Christine M. Loescher, Andreas Unger, Franziska Koser, Annika J. Klotz, Lena Wildschütz, Lydia Wachsmuth, Susanne Hille, Michaela M. Door, Anne Helfen, Richard Holtmeier, Cornelius Faber, Jonathan A. Kirk, Verena Hoerr, Oliver J. Müller, Wolfgang A. Linke

{"title":"Selective titin cleavage disrupts cardiac mechanical homeostasis to drive heart failure and fibrosis","authors":"Johanna K. Freundt, Paulina Hartmann, Christine M. Loescher, Andreas Unger, Franziska Koser, Annika J. Klotz, Lena Wildschütz, Lydia Wachsmuth, Susanne Hille, Michaela M. Door, Anne Helfen, Richard Holtmeier, Cornelius Faber, Jonathan A. Kirk, Verena Hoerr, Oliver J. Müller, Wolfgang A. Linke","doi":"10.1038/s44161-026-00829-z","DOIUrl":"10.1038/s44161-026-00829-z","url":null,"abstract":"Titin, the largest human protein, forms the elastic sarcomeric backbone, providing passive stiffness and length-dependent activation in cardiomyocytes. Whereas titin mutations cause inherited cardiomyopathies, ischemic and chemotherapy-induced injury also provoke proteolytic cleavage of titin’s elastic segment. However, the effects of acute titin stiffness loss remain unknown. Here we develop a knock-in mouse enabling in vivo cleavage of cardiac titin springs and use multimodal analysis (cardiac magnetic resonance imaging, echocardiography, microscopy, omics) to show that titin cleavage does not dilate the heart but reduces chamber size and impairs ventricular filling. Mechanical assays of isolated cardiomyocytes reveal diminished restoring forces causing a loss of elastic recoil. In vivo cleavage disrupts junctions, including integrin linkages and connexin 43 gap junctions, widens intermyocyte space without hypertrophy or hyperplasia and drives fibroblast activation, extracellular matrix remodeling and fibrosis. Compensatory mechanisms fail, leading to decompensated heart failure. These findings establish that proteolytic titin cleavage perturbs cardiac mechanical homeostasis, driving disease and matrix stiffening. Freundt, Hartmann and colleagues use a multimodal approach to show that titin cleavage impairs ventricular filling and reduces chamber size by disrupting elastic recoil, promotes fibroblast activation and ultimately drives decompensated heart failure, supporting a function of titin as a mechanical stress sensor.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 6","pages":"572-587"},"PeriodicalIF":12.6,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-026-00829-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262034","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

Multi-omic analysis of deep learning-derived phenotypes links ophthalmic imaging to cardiovascular and neurological traits 深度学习衍生表型的多组学分析将眼科成像与心血管和神经学特征联系起来

IF 12.6

Nature cardiovascular research Pub Date : 2026-06-16 DOI: 10.1038/s44161-026-00815-5

Thomas H. Julian, Haoran Dou, Jinming Duan, Jinghan Huang, Esther Yoo, David J. Green, Andrew Strange, Elham Alhathli, Matthew Sperrin, Pearse A. Keane, Emily Y. Chew, Bernard Keavney, Tomas W. Fitzgerald, Johnathan Cooper-Knock, Ewan Birney, Alejandro F. Frangi, Panagiotis I. Sergouniotis, on behalf of the UK Biobank Eye and Vision Consortium

{"title":"Multi-omic analysis of deep learning-derived phenotypes links ophthalmic imaging to cardiovascular and neurological traits","authors":"Thomas H. Julian, Haoran Dou, Jinming Duan, Jinghan Huang, Esther Yoo, David J. Green, Andrew Strange, Elham Alhathli, Matthew Sperrin, Pearse A. Keane, Emily Y. Chew, Bernard Keavney, Tomas W. Fitzgerald, Johnathan Cooper-Knock, Ewan Birney, Alejandro F. Frangi, Panagiotis I. Sergouniotis, on behalf of the UK Biobank Eye and Vision Consortium","doi":"10.1038/s44161-026-00815-5","DOIUrl":"10.1038/s44161-026-00815-5","url":null,"abstract":"The eye is a recognized source of biomarkers for cardiovascular and neurodegenerative disease risk. Here we characterize the breadth of these associations and identify biological axes that may mediate them. Using UK Biobank data, we developed a multi-omic analysis pipeline integrating physiological, radiomic, metabolomic and genomic information. We trained retinal adversarial autoencoders to represent optical coherence tomography images and color fundus photographs as 256-dimensional embeddings. Retinal adversarial autoencoder-derived embeddings were associated with a range of cardiovascular and neurodegenerative diseases, including ischemic heart disease, cerebrovascular disease, Parkinson’s disease and dementia. Examining associations across diverse omics datasets, we provide evidence linking ophthalmic imaging features to neurological and cardiovascular anatomy and function, lipid metabolism and gene sets associated with neurodegenerative pathology. Collectively, our findings show that ophthalmic features reflect complex, multisystem biological processes and reinforce the role of the eye as a composite indicator of systemic health. Julian et al. combine machine learning and multi-omic analyses using UK Biobank data to link ophthalmic image features to cardiovascular and neurodegenerative diseases and identify relevant pathways.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 6","pages":"541-554"},"PeriodicalIF":12.6,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-026-00815-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262035","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

Genetic perspectives on the comorbidity of anxiety and mood disorders with cardiovascular disease 焦虑和情绪障碍与心血管疾病共病的遗传学观点。

IF 12.6

Nature cardiovascular research Pub Date : 2026-06-08 DOI: 10.1038/s44161-026-00822-6

Eco J. C. de Geus, Jorien L. Treur, Brenda W. J. H. Penninx

{"title":"Genetic perspectives on the comorbidity of anxiety and mood disorders with cardiovascular disease","authors":"Eco J. C. de Geus, Jorien L. Treur, Brenda W. J. H. Penninx","doi":"10.1038/s44161-026-00822-6","DOIUrl":"10.1038/s44161-026-00822-6","url":null,"abstract":"An increasing concern in healthcare is the co-occurrence of mental and somatic disorders in patients, illustrated most prominently by the comorbidity of anxiety and mood disorders (AMD) with cardiovascular disease (CVD). Here we show that this comorbidity is largely mediated by genetic and environmental effects on risk mechanisms from the biological, behavioral, psychological and social domains shared by AMD and CVD. Genetically informative designs support the causal effects of AMD on the risk of CVD but show no evidence of reverse causality. This aligns with meta-analyses of randomized controlled trials that support positive effects of AMD treatment on CVD but find no consistent effects in the opposite direction. We suggest that patients with both CVD and AMD would benefit from a collaborative care approach. Interventions should focus on modifiable shared risk factors for both conditions, with lifestyle improvement and stress management appearing most promising. de Geus et al. review the comorbidity between anxiety and mood disorders and cardiovascular disease through a genetic lens, discussing the interaction between genetic components and shared risk factors in disease associations.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 6","pages":"508-525"},"PeriodicalIF":12.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207121","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

A world of possibilities for cardiac simulations 心脏模拟的无限可能。

IF 12.6

Nature cardiovascular research Pub Date : 2026-06-04 DOI: 10.1038/s44161-026-00830-6

Andrea Tavosanis

引用次数: 0

Genome-wide association study of coronary flow reserve assessed by cardiac perfusion PET suggests a role for NF-κB pathway 心肌灌注PET评估冠状动脉血流储备的全基因组关联研究提示NF-κB通路的作用。

IF 12.6

Nature cardiovascular research Pub Date : 2026-06-02 DOI: 10.1038/s44161-026-00819-1

Rasika Venkatesh, Tess Cherlin, Nicole Wayne, Rachit Kumar, Lindsay Guare, Venkata P. Singamneni, Brett Irving, Scott Dudek, Penn Medicine BioBank, Michael G. Levin, Shefali Setia-Verma, Marie A. Guerraty

{"title":"Genome-wide association study of coronary flow reserve assessed by cardiac perfusion PET suggests a role for NF-κB pathway","authors":"Rasika Venkatesh, Tess Cherlin, Nicole Wayne, Rachit Kumar, Lindsay Guare, Venkata P. Singamneni, Brett Irving, Scott Dudek, Penn Medicine BioBank, Michael G. Levin, Shefali Setia-Verma, Marie A. Guerraty","doi":"10.1038/s44161-026-00819-1","DOIUrl":"10.1038/s44161-026-00819-1","url":null,"abstract":"Coronary microvascular disease (CMVD) contributes to the large burden of ischemic heart disease (IHD), and there is a need for mechanistic insight and targeted therapies. Perfusion cardiac PET allows for the quantitative assessment of coronary flow reserve (CFR), which reflects coronary microvascular function. Here we use cardiac PET CFR as a measure of CMVD to perform first a gene association study with previously reported IHD loci and, second, an exploratory genome-wide association study. Of 241 known IHD loci, we identify 45 and 18 loci that are associated with CFR in populations genetically similar to African and European populations, respectively. We then perform a genome-wide association study followed by downstream and pathway analyses and identified an association between loci associated with CFR and the NF-κB pathway. We support these associations with targeted proteomic data. Our multi-omic analyses identified potential CMVD loci and suggest a role for the NF-κB pathway in CMVD. Venkatesh, Cherlin et al. perform a genome-wide association study to identify variants associated with myocardial blood flow reserve as a readout of coronary microvascular function, revealing NF-kB signaling as a potential regulator.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 6","pages":"555-564"},"PeriodicalIF":12.6,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-026-00819-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148152459","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

Lipoprotein(a) and oxidized phospholipids are associated with myocardial inflammation after acute myocardial infarction 脂蛋白(a)和氧化磷脂与急性心肌梗死后心肌炎症有关。

IF 12.6

Nature cardiovascular research Pub Date : 2026-05-29 DOI: 10.1038/s44161-026-00821-7

Mark Atallah, Nadim Nasrallah, Tarek Harb, Ines Valenta, Thomas H. Schindler, Amelia S. Wallace, Sotirios Tsimikas, Gary Gerstenblith, Thorsten M. Leucker

{"title":"Lipoprotein(a) and oxidized phospholipids are associated with myocardial inflammation after acute myocardial infarction","authors":"Mark Atallah, Nadim Nasrallah, Tarek Harb, Ines Valenta, Thomas H. Schindler, Amelia S. Wallace, Sotirios Tsimikas, Gary Gerstenblith, Thorsten M. Leucker","doi":"10.1038/s44161-026-00821-7","DOIUrl":"10.1038/s44161-026-00821-7","url":null,"abstract":"Localized myocardial inflammation after acute myocardial infarction (MI) is regulated by innate immune pathways. Oxidized phospholipids (OxPLs) carried on lipoprotein(a) (Lp(a)) are proinflammatory, but their association with myocardial inflammation during the early post-MI period has not been described. Here we study patients enrolled in a randomized, double-blind trial of in-hospital PCSK9 inhibition versus placebo, in whom this treatment decreased myocardial inflammation after MI. We analyze plasma levels of OxPLs on apolipoprotein B-100 containing lipoproteins (OxPL-apoB), OxPLs on apolipoprotein(a) (OxPL-apo(a)), and Lp(a) during hospital admission and at 30 days, and paired [18F]-fluorodeoxyglucose positron emission tomography of myocardial inflammatory activity. Higher levels of OxPL-apoB, OxPL-apo(a) and Lp(a) at 30 days were associated with greater myocardial inflammatory activity; changes in Lp(a) and OxPL-apoB from baseline to 30 days were positively correlated with the change in myocardial [18F]-fluorodeoxyglucose uptake. These findings demonstrate that Lp(a) and OxPL are associated with persistent myocardial inflammation after an acute MI. Atallah et al. show that oxidized phospholipids and lipoprotein (a), but not systemic inflammation indicators are associated with tissue-level myocardial inflammation after infarction.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 6","pages":"565-571"},"PeriodicalIF":12.6,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148058814","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

Consensus statement on mass spectrometry-based proteomic analysis of cardiac tissue 基于质谱的心脏组织蛋白质组学分析的共识声明。

IF 12.6

Nature cardiovascular research Pub Date : 2026-05-25 DOI: 10.1038/s44161-026-00824-4

Alicia Lundby, Jennifer E. Van Eyk, Manuel Mayr, Melanie Y. White, Jonathan A. Kirk, Jonathan S. Achter, Justyna Fert-Bober, Michael Wierer, Philipp Mertins, Maggie P. Y. Lam, Sean J. Humphrey, Edward Lau, Anthony O. Gramolini, Ying Ge, Rebekah L. Gundry

{"title":"Consensus statement on mass spectrometry-based proteomic analysis of cardiac tissue","authors":"Alicia Lundby, Jennifer E. Van Eyk, Manuel Mayr, Melanie Y. White, Jonathan A. Kirk, Jonathan S. Achter, Justyna Fert-Bober, Michael Wierer, Philipp Mertins, Maggie P. Y. Lam, Sean J. Humphrey, Edward Lau, Anthony O. Gramolini, Ying Ge, Rebekah L. Gundry","doi":"10.1038/s44161-026-00824-4","DOIUrl":"10.1038/s44161-026-00824-4","url":null,"abstract":"Mass spectrometry-based cardiac proteomics provides direct molecular insight into cardiac physiology and disease. While plasma proteomics has advanced biomarker discovery, the analysis of cardiac tissue is essential for mechanistic understanding and therapeutic target identification; however, proteomic investigation of cardiac tissue faces unique challenges, including limited sample availability, regional heterogeneity, variability in collection and processing, and inconsistent reporting practices that hinder reproducibility and data integration. Here, we provide a practical framework for designing and conducting mass spectrometry-based proteomic studies of cardiac tissue and primary cardiac cells. We outline best practices and key considerations for sample handling, experimental design, data acquisition, quality control and statistical analysis. This guideline aims to support cardiac researchers in generating robust and reproducible proteomics datasets that advance our understanding of cardiac biology in both physiological and pathological contexts. This Consensus Statement provides practical guidance for mass spectrometry-based proteomic analyses of cardiac tissue samples. It defines best practices across the experimental workflow to enable reproducible, high-quality datasets.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 6","pages":"526-540"},"PeriodicalIF":12.6,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-026-00824-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019155","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

CAMK2 inhibition treats genetic dilated cardiomyopathy in mice CAMK2抑制对小鼠遗传性扩张型心肌病的治疗作用。

IF 12.6

Nature cardiovascular research Pub Date : 2026-05-21 DOI: 10.1038/s44161-026-00826-2

引用次数: 0

Single-cell and spatial transcriptomics identify immune–stromal interactions in cardiac allograft vasculopathy 单细胞和空间转录组学鉴定同种异体心脏移植血管病变中免疫-基质相互作用

IF 10.8

Nature cardiovascular research Pub Date : 2026-05-18 DOI: 10.1038/s44161-026-00813-7

Macee C. Owen, Daniel Yuhang Li, Haewon Shin, Wenduo Gu, Alekhya Parvathaneni, Farid F. Kadyrov, Xiaoran Wang, Maura Sticco-Ivins, Gianni Bonnici, Samantha L. Nelson, Hao Dun, Sariah Hyacinth, Samantha C. Giangrasso, Caroline Chou, Chieh-Yu Lin, Michael T. Cain, Albert Pedroza, Alex Dalal, Karim Sallam, Jack Boyd, Joseph Woo, Junedh M. Amrute, Paul Cheng, Kory J. Lavine, Benjamin J. Kopecky

{"title":"Single-cell and spatial transcriptomics identify immune–stromal interactions in cardiac allograft vasculopathy","authors":"Macee C. Owen, Daniel Yuhang Li, Haewon Shin, Wenduo Gu, Alekhya Parvathaneni, Farid F. Kadyrov, Xiaoran Wang, Maura Sticco-Ivins, Gianni Bonnici, Samantha L. Nelson, Hao Dun, Sariah Hyacinth, Samantha C. Giangrasso, Caroline Chou, Chieh-Yu Lin, Michael T. Cain, Albert Pedroza, Alex Dalal, Karim Sallam, Jack Boyd, Joseph Woo, Junedh M. Amrute, Paul Cheng, Kory J. Lavine, Benjamin J. Kopecky","doi":"10.1038/s44161-026-00813-7","DOIUrl":"10.1038/s44161-026-00813-7","url":null,"abstract":"Cardiac allograft vasculopathy (CAV) is the leading cause of mortality after heart transplantation, yet no targeted therapies exist to prevent or reverse disease progression, and patients with CAV ultimately require a retransplant. CAV is characterized by progressive neointimal hyperplasia in donor coronary arteries, resulting in luminal occlusion and eventual allograft failure. Although immune and stromal cell interactions are thought to drive disease, the key cellular and molecular mechanisms remain poorly defined. Here we integrate single-cell RNA sequencing and spatial transcriptomics of human coronary arteries to characterize the CAV neointimal microenvironment. By comparing arteries with CAV with atherosclerotic coronary artery disease and non-diseased controls, we identify a distinct transcriptional signature of CAV. Our analysis reveals that modulated vascular smooth muscle cells and macrophage subsets dominate the neointima and interact to promote type 1 interferon (IFN)-mediated inflammation. Using a mouse model of CAV, we show that IFN signaling blockade with ruxolitinib significantly reduces CAV incidence and prolongs allograft survival. These findings define key cellular drivers of CAV and highlight IFN signaling as a potential therapeutic target. Owen et al. used single-cell RNA sequencing and spatial transcriptomics to analyze graft cells in heart transplants with cardiac allograft vasculopathy, showing that vascular smooth muscle cells and macrophages drive interferon-mediated inflammation and that JAK signaling blockade prolongs allograft survival.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 5","pages":"439-455"},"PeriodicalIF":10.8,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147968211","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

Macrophages orchestrate the landscape of advanced cardiac allograft vasculopathy 巨噬细胞调控晚期异体心脏移植血管病变的景观

IF 10.8

Nature cardiovascular research Pub Date : 2026-05-18 DOI: 10.1038/s44161-026-00814-6

Eleni Tseliou, Stavros G. Drakos, Edward B. Thorp

引用次数: 0