Nature cardiovascular research最新文献

{"title":"The cellular and molecular cardiac tissue responses in human inflammatory cardiomyopathies after SARS-CoV-2 infection and COVID-19 vaccination.","authors":"Henrike Maatz, Eric L Lindberg, Eleonora Adami, Natalia López-Anguita, Alvaro Perdomo-Sabogal, Lucía Cocera Ortega, Giannino Patone, Daniel Reichart, Anna Myronova, Sabine Schmidt, Ahmed Elsanhoury, Oliver Klein, Uwe Kühl, Emanuel Wyler, Markus Landthaler, Schayan Yousefian, Simon Haas, Florian Kurth, Sarah A Teichmann, Gavin Y Oudit, Hendrik Milting, Michela Noseda, Jonathan G Seidman, Christine E Seidman, Bettina Heidecker, Leif E Sander, Birgit Sawitzki, Karin Klingel, Patrick Doeblin, Sebastian Kelle, Sophie Van Linthout, Norbert Hubner, Carsten Tschöpe","doi":"10.1038/s44161-025-00612-6","DOIUrl":"https://doi.org/10.1038/s44161-025-00612-6","url":null,"abstract":"<p><p>Myocarditis, characterized by inflammatory cell infiltration, can have multiple etiologies, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or, rarely, mRNA-based coronavirus disease 2019 (COVID-19) vaccination. The underlying cellular and molecular mechanisms remain poorly understood. In this study, we performed single-nucleus RNA sequencing on left ventricular endomyocardial biopsies from patients with myocarditis unrelated to COVID-19 (Non-COVID-19), after SARS-CoV-2 infection (Post-COVID-19) and after COVID-19 vaccination (Post-Vaccination). We identified distinct cytokine expression patterns, with interferon-γ playing a key role in Post-COVID-19, and upregulated IL16 and IL18 expression serving as a hallmark of Post-Vaccination myocarditis. Although myeloid responses were similar across all groups, the Post-Vaccination group showed a higher proportion of CD4⁺ T cells, and the Post-COVID-19 group exhibited an expansion of cytotoxic CD8⁺ T and natural killer cells. Endothelial cells showed gene expression changes indicative of vascular barrier dysfunction in the Post-COVID-19 group and ongoing angiogenesis across all groups. These findings highlight shared and distinct mechanisms driving myocarditis in patients with and without a history of SARS-CoV-2 infection or vaccination.</p>","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494999","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":"TRPM7 channel as a potential therapeutic target for AAA","authors":"Ryan Laloo,&nbsp;Marc Bailey","doi":"10.1038/s44161-024-00598-7","DOIUrl":"10.1038/s44161-024-00598-7","url":null,"abstract":"TRPM7 channel interference protects against abdominal aortic aneurysm (AAA) formation and progression in mice by regulating phenotypic switching of vascular smooth muscle cells, extracellular matrix degradation and vessel wall inflammation, all of which are hallmark features of abdominal aortic aneurysm pathogenesis.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 2","pages":"126-128"},"PeriodicalIF":9.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424380","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":"TRPM7 channel activity promotes the pathogenesis of abdominal aortic aneurysms","authors":"Pengyu Zong,&nbsp;Cindy X. Li,&nbsp;Jianlin Feng,&nbsp;Zhichao Yue,&nbsp;Thushara Nethramangalath,&nbsp;Yangzhouyun Xie,&nbsp;Xin Qin,&nbsp;Mara Cicchetti,&nbsp;Yujun Cai,&nbsp;Evan Jellison,&nbsp;Masayuki Matsushita,&nbsp;Loren W. Runnels,&nbsp;Lixia Yue","doi":"10.1038/s44161-024-00596-9","DOIUrl":"10.1038/s44161-024-00596-9","url":null,"abstract":"Abdominal aortic aneurysms (AAAs) occur in 1–2% of the elderly. The rupture of an AAA usually causes uncontrollable lethal hemorrhage, and its risk increases with AAA size. However, there is no effective pharmacological therapy for hindering AAA growth. Here we show that global or vascular smooth muscle cell (VSMC)-specific transient receptor potential melastatin 7 (TRPM7) knockout in mice prevented AAA formation, as indicated by inhibited VSMC reprogramming, reduced inflammatory infiltration and suppressed matrix degradation. Mechanistically, we showed that TRPM7-mediated Ca2+ signaling promotes Kruppel-like factor 4 (KLF4) activation, driving VSMC reprogramming and accelerating AAA growth. By generating channel-dead and using kinase-inactive knockin mice, we found that it is the channel function, rather than kinase activity, that is required for TRPM7-mediated AAA pathogenesis. Importantly, TRPM7 inhibitor NS8593 suppressed VSMC reprogramming and protected mice against AAA formation. Our data suggest that TRPM7 is a promising therapeutic target for developing effective prophylactic medications to limit AAA progression. In addition, the channel-dead TRPM7 knockin mice will serve as a valuable tool for elucidating the roles of TRPM7 in other pathophysiological conditions. Zong et al. reveal that genetic and pharmacologic inhibition of TRPM7 channel function prevents the activation of Ca2+–CaM–calcineurin–KLF4 signaling, the phenotypic switch of vascular smooth muscle cells and the formation of abdominal aortic aneurysms.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 2","pages":"197-215"},"PeriodicalIF":9.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424332","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":"The TRPM7 chanzyme in smooth muscle cells drives abdominal aortic aneurysm in mice","authors":"Xuan Wang,&nbsp;Mi Wang,&nbsp;Tian-Tian Zhu,&nbsp;Zi-Jie Zheng,&nbsp;Shuang Li,&nbsp;Zhao-Yi Sui,&nbsp;Xin Guo,&nbsp;Sha Wu,&nbsp;Nai-Ning Zhang,&nbsp;Zhi-Yi Yu,&nbsp;Chang-Ping Hu,&nbsp;Yong-Bo Tang,&nbsp;Qing Wang,&nbsp;Zheng Zhang","doi":"10.1038/s44161-025-00613-5","DOIUrl":"10.1038/s44161-025-00613-5","url":null,"abstract":"Ionic signaling in smooth muscle cells (SMCs) is critical for vascular homeostasis. In this study, we untangled the role of the bifunctional TRPM7 channel kinase (chanzyme) in abdominal aortic aneurysm (AAA) pathogenesis. Comparing SMC-specific, macrophage-specific and endothelial cell–specific Trpm7 knockout, we revealed that SMC-specific Trpm7 deficiency protected mice from AAA in two distinct preclinical models of the disease. We showed that the TRPM7 channel activity increased the Ca2+ and Zn2+ influx and the Ca2+/calcineurin/CRTC2/CREB-dependent and Zn2+/MTF1-dependent Mmp2 transcription. Repurposing the clinical drug FTY720 to prevent and treat AAA resulted in improved aortic phenotypes through inhibition of TRPM7 channel activity. This study highlights the ionic mechanisms underlying AAA, identifies TRPM7 as a potential therapeutic target and suggests that blocking TRPM7 channels could be a viable strategy for treating AAA. Wang et al. demonstrate that the vascular smooth muscle cell–dependent expression of TRPM7, an ion channel with kinase function, increases the levels of calcium and zinc and, thus, increases the MMP2 activity and contributes to the formation of abdominal aortic aneurysm.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 2","pages":"216-234"},"PeriodicalIF":9.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424329","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":"Long-term survival and durable recovery of heart failure in patients with triglyceride deposit cardiomyovasculopathy treated with tricaprin.","authors":"Ken-Ichi Hirano, Satomi Okamura, Koichiro Sugimura, Hideyuki Miyauchi, Yusuke Nakano, Kotaro Nochioka, Chikako Hashimoto, Yoshitaka Iwanaga, Kenichi Nakajima, Satoshi Yamaguchi, Yoko Yasui, Shinsaku Shimamoto, Makito Hirano, Mana Okune, Yuki Nishimura, Hisashi Shimoyama, Yasuyuki Nagasawa, Tetsuya Amano, Shimpei Kuniyoshi, Shu-Ping Hui, Nobuhiro Zaima, Yoshihiko Ikeda, Tomomi Yamada, Shinichiro Fujimoto, Yasuhiko Sakata, Kunihisa Kobayashi","doi":"10.1038/s44161-025-00611-7","DOIUrl":"https://doi.org/10.1038/s44161-025-00611-7","url":null,"abstract":"<p><p>Heart disease is a major global threat. Triglyceride deposit cardiomyovasculopathy (TGCV) is an emerging, noncommunicable, adult-onset heart disease, first identified in Japanese patients with heart failure (HF) requiring cardiac transplantation^1-3. In TGCV, defective intracellular lipolysis of long-chain triglycerides (TGs) results in cellular steatosis and energy failure mainly in cardiomyocytes⁴ and smooth muscle cells⁵, leading to HF, diffuse coronary artery disease with TG deposition and ventricular arrhythmias with high mortality⁶. Tricaprin, a class of medium-chain TGs, recently corrected myocardial TG lipolysis⁷. Here we report remarkable long-term survival and durable recovery of HF in patients with TGCV treated with supplemental tricaprin in registry studies. Our study offers a classification of heart disease caused by defective lipolysis and its possible practical treatment. Because myocardial lipid droplets are a common feature in HF and their potential as therapeutic targets has been discussed worldwide, our findings warrant investigation into other ethnicities.</p>","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416504","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":"IL-1β enhances susceptibility to atrial fibrillation in mice by acting through resident macrophages and promoting caspase-1 expression.","authors":"Oscar Moreno-Loaiza, Vinicius Cardoso Soares, Manuela de Assumpção Souza, Narendra Vera-Nuñez, Ainhoa Rodriguez de Yurre Guirao, Tatiana Pereira da Silva, Ana Beatriz Pozes, Larissa Perticarrari, Evelin Monteiro, Maria Clara Albino, Sophia Barros Silva, Suelen Silva Gomes Dias, Leonardo Maciel, Humberto Muzi-Filho, Dahienne Ferreira de Oliveira, Bruno Cabral Braga, Luan Pereira Diniz, Mario Costa Cruz, Simone Reis Barbosa, Archimedes Barbosa Castro-Junior, Luciana Conde, Mauro Jorge Cabral-Castro, Olga Ferreira de Souza, Martha Valéria Tavares Pinheiro, Nilson Araújo de Oliveira Junior, Leonardo Rezende de Siqueira, Rodrigo Periquito Cosenza, Claudio Munhoz da Fontoura, Jose Carlos Pizzolante Secco, Juliana da Rocha Ferreira, Andréa Silvestre de Sousa, Denilson Albuquerque, Ronir Raggio Luiz, Pedro Nicolau-Neto, Marco Antonio Pretti, Mariana Boroni, Martin Hernán Bonamino, Tais Hanae Kasai-Brunswick, Debora Bastos Mello, Triciana Gonçalves-Silva, Isalira Peroba Ramos, Fernando A Bozza, João Paulo do Vale Madeiro, Roberto Coury Pedrosa, Marcela Sorelli Carneiro-Ramos, Herculano da Silva Martinho, Patrícia T Bozza, Fernanda Mesquita de Souza, Gabriel Victor Lucena da Silva, Thiago M Cunha, Ilija Uzelac, Flavio Fenton, Renata Moll-Bernardes, Claudia N Paiva, Ariel L Escobar, Emiliano Medei","doi":"10.1038/s44161-025-00610-8","DOIUrl":"https://doi.org/10.1038/s44161-025-00610-8","url":null,"abstract":"<p><p>Atrial fibrillation (AF) is more prevalent in patients with elevated interleukin (IL)-1β levels. Here we show that daily administration of IL-1β for 15 days sensitizes mice to AF, leading to fibrosis, accumulation of β-pleated sheet proteins in the left atrium, and systemic inflammation, resembling the pathophysiological changes observed in patients with AF. IL-1β administration creates a positive feedback loop, dependent on the IL-1 receptor (IL-1R) activity in cardiac resident macrophages. This results in increased caspase-1 maturation in the left atrium and elevated Il1b and Casp1 transcription in atrial macrophages. IL-1β treatment accelerated action potential and Ca²⁺ restitution in the left atrium, leading to action-potential shortening. This, along with increased caspase-1 maturation and IL-1R signaling, was essential for inducing AF. Lack of IL-1R in macrophages, but not cardiomyocytes, prevented IL-1β-induced AF sensitivity. By depleting recruited macrophages or deleting IL-1R specifically in cardiac resident macrophages, we further demonstrate that IL-1β/IL-1R signaling in these resident macrophages is responsible for increased AF susceptibility. These findings offer insights into the therapeutic potential of targeting IL-1β/IL-1R signaling in patients with AF and emphasize the importance of recognizing different underlying causes in this patient group.</p>","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366962","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":"Large-scale multi-omics identifies drug targets for heart failure with reduced and preserved ejection fraction.","authors":"Danielle Rasooly, Claudia Giambartolomei, Gina M Peloso, Hesam Dashti, Brian R Ferolito, Daniel Golden, Andrea R V R Horimoto, Maik Pietzner, Eric H Farber-Eger, Quinn Stanton Wells, Giorgio Bini, Gabriele Proietti, Gian Gaetano Tartaglia, Nicole M Kosik, Peter W F Wilson, Lawrence S Phillips, Patricia B Munroe, Steffen E Petersen, Kelly Cho, J Michael Gaziano, Andrew R Leach, John Whittaker, Claudia Langenberg, Nay Aung, Yan V Sun, Alexandre C Pereira, Juan P Casas, Jacob Joseph","doi":"10.1038/s44161-025-00609-1","DOIUrl":"https://doi.org/10.1038/s44161-025-00609-1","url":null,"abstract":"<p><p>Heart failure (HF) has limited therapeutic options. In this study, we differentiated the pathophysiological underpinnings of the HF subtypes-HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)-and uncovered subtype-specific therapeutic strategies. We investigated the causal roles of the human proteome and transcriptome using Mendelian randomization on more than 420,000 participants from the Million Veteran Program (27,799 HFrEF and 27,579 HFpEF cases). We created therapeutic target profiles covering efficacy, safety, novelty, druggability and mechanism of action. We replicated findings on more than 175,000 participants of diverse ancestries. We identified 70 HFrEF and 10 HFpEF targets, of which 58 were not previously reported; notably, the HFrEF and HFpEF targets are non-overlapping, suggesting the need for subtype-specific therapies. We classified 14 previously unclassified HF loci as HFrEF. We substantiated the role of ubiquitin-proteasome system, small ubiquitin-related modifier pathway, inflammation and mitochondrial metabolism in HFrEF. Among druggable genes, IL6R, ADM and EDNRA emerged as potential HFrEF targets, and LPA emerged as a potential target for both subtypes.</p>","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366963","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":"Discovery of drug targets for heart failure with preserved and reduced ejection fraction.","authors":"Scott C Ritchie","doi":"10.1038/s44161-024-00605-x","DOIUrl":"https://doi.org/10.1038/s44161-024-00605-x","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366961","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":"Cardiovascular effects and safety of classic psychedelics","authors":"Acile Nahlawi,&nbsp;Leon M. Ptaszek,&nbsp;Jeremy N. Ruskin","doi":"10.1038/s44161-025-00608-2","DOIUrl":"10.1038/s44161-025-00608-2","url":null,"abstract":"Psychedelics, used for millennia in spiritual and healing practices, have emerged as promising treatments for mental health conditions including depression, post-traumatic stress disorder (PTSD), substance use disorders and anxiety. Despite the therapeutic potential of psychedelics and their increasing use in both medical and nonmedical settings, there is a paucity of data on their cardiovascular safety. Here we review current evidence on the cardiovascular effects and safety of this unique class of therapeutic agents. The cardiovascular effects and associated risks of classic psychedelics are categorized into three areas: electrophysiological effects and arrhythmia risk, structural effects and valvular heart disease risk, and vascular effects including hypertension and ischemia risks. The Review also emphasizes crucial knowledge gaps that require further basic and clinical investigation including studies in individuals with underlying cardiovascular disease, characterization of important drug–drug interactions and studies on the safety of repetitive, long-term (including microdosing) exposure to classic psychedelics. Nahlawi, Ptaszek and Ruskin review the implications of classic psychedelic use on the cardiovascular system and highlight their safety profiles and potential concerns to accompany their growing use in the clinic.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 2","pages":"131-144"},"PeriodicalIF":9.4,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257621","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":"Microplastics in the bloodstream can induce cerebral embolism and neurological impairment","authors":"Gerburg Schwaerzer","doi":"10.1038/s44161-025-00615-3","DOIUrl":"10.1038/s44161-025-00615-3","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"4 2","pages":"120-120"},"PeriodicalIF":9.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191500","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}