Nature cardiovascular research最新文献

Tolerogenic DCs expressing anti-FAP chimeric antigen receptor prevent adverse cardiac remodeling. 表达抗fap嵌合抗原受体的耐受性dc可预防不良的心脏重构。

IF 10.8

Nature cardiovascular research Pub Date : 2026-05-07 DOI: 10.1038/s44161-026-00823-5

Elisa Martini

引用次数: 0

High-resolution cardiac mapping meets computational imaging to merge structure and function. 高分辨率心脏测绘与计算机成像相结合，实现结构与功能的融合。

IF 10.8

Nature cardiovascular research Pub Date : 2026-05-05 DOI: 10.1038/s44161-026-00812-8

Bastiaan J Boukens, Daniël A Pijnappels

引用次数: 0

CAMK2D causes heart failure in mice with RBM20 cardiomyopathy. CAMK2D引起RBM20心肌病小鼠心力衰竭。

IF 10.8

Nature cardiovascular research Pub Date : 2026-05-04 DOI: 10.1038/s44161-026-00818-2

Maarten M G van den Hoogenhof, Javier Duran, Thiago Britto-Borges, Vasco Sequeira, Elena Kemmling, Laura Konrad, Friederike Schreiter, David C Lennermann, Joshua Hartmann, Laura Schraft, Julia Kornienko, Theresa Bock, Marcus Krüger, Christoph Maack, Christoph Dieterich, Lars M Steinmetz, Matthias Dewenter, Johannes Backs

{"title":"CAMK2D causes heart failure in mice with RBM20 cardiomyopathy.","authors":"Maarten M G van den Hoogenhof, Javier Duran, Thiago Britto-Borges, Vasco Sequeira, Elena Kemmling, Laura Konrad, Friederike Schreiter, David C Lennermann, Joshua Hartmann, Laura Schraft, Julia Kornienko, Theresa Bock, Marcus Krüger, Christoph Maack, Christoph Dieterich, Lars M Steinmetz, Matthias Dewenter, Johannes Backs","doi":"10.1038/s44161-026-00818-2","DOIUrl":"https://doi.org/10.1038/s44161-026-00818-2","url":null,"abstract":"Although heart disease arises from different etiologies, treatment remains largely one-size-fits-all, leaving many patients without optimal benefit, which highlights the need for cause-directed therapies. Pathogenic variants in RBM20, a cardiac splicing factor, lead to an aggressive form of dilated cardiomyopathy with high risk of ventricular arrhythmias. We hypothesized that the splicing target calcium/calmodulin-dependent kinase II delta (CAMK2D) is disease causing in RBM20 cardiomyopathy. Here we show that Rbm20/Camk2d double knockout mice are protected from heart failure and sudden cardiac death. In Rbm20-deficient hearts, phosphorylation of CAMK2D targets was increased, indicating that RBM20 loss results not only in mis-splicing of Camk2d transcripts but also in functional activation of CAMK2D signaling. Reexpression of individual CAMK2D splice variants in Rbm20/Camk2d double knockout mice reintroduced cardiac dysfunction, demonstrating that overactivation, rather than mis-splicing, drives disease. Treatment of Rbm20-p.Arg636Gln knockin mice with the ATP-competitive CAMK2 inhibitor hesperadin improved cardiac function. These findings identify CAMK2D overactivation as a central mechanism in RBM20 cardiomyopathy and support CAMK2D inhibition as a promising cause-directed therapy.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847229","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 NPR1 inhibitor XXB750 may worsen heart failure. NPR1抑制剂XXB750可能加重心力衰竭。

IF 10.8

Nature cardiovascular research Pub Date : 2026-05-04 DOI: 10.1038/s44161-026-00820-8

Andrea Tavosanis

引用次数: 0

Antibody-siRNA conjugates enable macrophage-specific osteopontin inhibition to suppress atrial fibrillation. 抗体- sirna偶联物使巨噬细胞特异性骨桥蛋白抑制抑制房颤。

IF 10.8

Nature cardiovascular research Pub Date : 2026-04-29 DOI: 10.1038/s44161-026-00808-4

Na Li

引用次数: 0

Mechanisms and therapeutic potential of colchicine in atherosclerotic cardiovascular disease. 秋水仙碱在动脉粥样硬化性心血管疾病中的作用机制及治疗潜力。

IF 10.8

Nature cardiovascular research Pub Date : 2026-04-27 DOI: 10.1038/s44161-026-00807-5

Xinyi Xia, Fen Yang, Yuhan Liao, Jiyu Zhang, Junyi He, Miao Yu, Xiang Cheng

{"title":"Mechanisms and therapeutic potential of colchicine in atherosclerotic cardiovascular disease.","authors":"Xinyi Xia, Fen Yang, Yuhan Liao, Jiyu Zhang, Junyi He, Miao Yu, Xiang Cheng","doi":"10.1038/s44161-026-00807-5","DOIUrl":"https://doi.org/10.1038/s44161-026-00807-5","url":null,"abstract":"Over the past decade, colchicine has re-emerged as a promising therapeutic candidate for atherosclerotic cardiovascular disease. Here we review evidence from large randomized controlled trials together with advances in mechanistic research that have clarified how colchicine modulates vascular inflammation and plaque stability. Canonically, colchicine disrupts microtubule dynamics and suppresses NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation. Beyond these actions, it limits oxidative stress, modulates cytoskeletal cross-talk, attenuates cholesterol crystal formation and reprograms inflammatory and metabolic proteomic networks. Colchicine influences multiple vascular and immune cell types, including neutrophils, monocytes, macrophages, endothelial cells, smooth muscle cells and platelets, collectively reducing vascular inflammation and promoting plaque stability. Notably, while colchicine has demonstrated benefit in coronary artery disease, several recent trials in cerebrovascular disease have reported neutral outcomes, suggesting disease-specific inflammatory mechanisms and therapeutic responsiveness. Integrating mechanistic insights with clinical evidence will be critical to optimize colchicine use and advance precision anti-inflammatory strategies in atherosclerotic cardiovascular disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791484","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

Therapeutic Spp1 silencing in TREM2⁺ cardiac macrophages suppresses atrial fibrillation. 治疗性沉默TREM2+心脏巨噬细胞中的Spp1抑制心房颤动。

IF 10.8

Nature cardiovascular research Pub Date : 2026-04-23 DOI: 10.1038/s44161-026-00806-6

Noor Momin, Steffen Pabel, Arnab Rudra, Nina Kumowski, I-Hsiu Lee, Hana Seung, Kyle I Mentkowski, Aneesh Bapat, Masahiro Yamazoe, Laura Stengel, Charlotte G Muse, Alexandre Paccalet, Farid F Kadyrov, Cristina González-Correa, Emily Jacobs, Ellie Feng, Jisoo Park, Jana Grune, Maximilian J Schloss, Samuel Sossalla, Gregory Wojtkiewicz, Yoshiko Iwamoto, Patrick McMullen, Richard N Mitchell, Patrick T Ellinor, Daniel G Anderson, Kamila Naxerova, Matthias Nahrendorf, Maarten Hulsmans

{"title":"Therapeutic Spp1 silencing in TREM2+ cardiac macrophages suppresses atrial fibrillation.","authors":"Noor Momin, Steffen Pabel, Arnab Rudra, Nina Kumowski, I-Hsiu Lee, Hana Seung, Kyle I Mentkowski, Aneesh Bapat, Masahiro Yamazoe, Laura Stengel, Charlotte G Muse, Alexandre Paccalet, Farid F Kadyrov, Cristina González-Correa, Emily Jacobs, Ellie Feng, Jisoo Park, Jana Grune, Maximilian J Schloss, Samuel Sossalla, Gregory Wojtkiewicz, Yoshiko Iwamoto, Patrick McMullen, Richard N Mitchell, Patrick T Ellinor, Daniel G Anderson, Kamila Naxerova, Matthias Nahrendorf, Maarten Hulsmans","doi":"10.1038/s44161-026-00806-6","DOIUrl":"10.1038/s44161-026-00806-6","url":null,"abstract":"Atrial fibrillation and the risk of its lethal complications are propelled by fibrosis, which induces electrical heterogeneity and gives rise to reentry circuits. Atrial TREM2+ macrophages secrete osteopontin (encoded by Spp1), a matricellular signaling protein that engenders fibrosis, inflammation, and atrial fibrillation. Here we developed an antibody-siRNA conjugate (ARC) drug candidate to silence Spp1. The ARC relies on an anti-TREM2 antibody for delivering Spp1-targeted siRNA to a pathogenic macrophage subset that expands in human atrial fibrillation. The ARC preferentially targeted atrial TREM2+ macrophages with limited uptake by other immune or stromal cells of the heart. We observed efficient silencing of the target gene in human myocardium and in mice, where it reduced pro-fibrotic fibroblast activation and atrial fibrosis. Four weeks of systemic ARC treatment suppressed inducible atrial fibrillation in mice exposed to clinically prevalent risk factors. These results suggest that macrophage subset targeting offers a viable immunomodulatory strategy for atrial fibrillation.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791541","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

PCBP1 regulates alternative splicing of AARS2 in congenital cardiomyopathy PCBP1调节先天性心肌病中AARS2的选择性剪接

IF 10.8

Nature cardiovascular research Pub Date : 2026-04-20 DOI: 10.1038/s44161-026-00798-3

Yao Wei Lu, Zhuomin Liang, Kerry Dorr, Samantha Ruiz, Xiaoran Huang, Denise Fangnibo Hanvi, Sheri M. Juntilla, Gisela Beutner, Shuhan Lyu, Haipeng Guo, Tiago Fernandes, Ramon A. Espinoza-Lewis, Tingting Wang, Kathryn Li, Xue Li, Gurinder Bir Singh, Yi Wang, Rui Deng, Douglas Cowan, John D. Mably, William T. Pu, Jessie Huang, George A. Porter Jr., Frank Conlon, Hong Chen, Da-Zhi Wang

{"title":"PCBP1 regulates alternative splicing of AARS2 in congenital cardiomyopathy","authors":"Yao Wei Lu, Zhuomin Liang, Kerry Dorr, Samantha Ruiz, Xiaoran Huang, Denise Fangnibo Hanvi, Sheri M. Juntilla, Gisela Beutner, Shuhan Lyu, Haipeng Guo, Tiago Fernandes, Ramon A. Espinoza-Lewis, Tingting Wang, Kathryn Li, Xue Li, Gurinder Bir Singh, Yi Wang, Rui Deng, Douglas Cowan, John D. Mably, William T. Pu, Jessie Huang, George A. Porter Jr., Frank Conlon, Hong Chen, Da-Zhi Wang","doi":"10.1038/s44161-026-00798-3","DOIUrl":"10.1038/s44161-026-00798-3","url":null,"abstract":"Mutations in the AARS2 gene are linked to infantile cardiomyopathy; however, the underlying molecular mechanism remains unknown. Here we report that PCBP1, a poly(rC) binding protein, interacts with the AARS2 transcript to mediate its alternative splicing. Cardiomyocyte-specific deletion of Pcbp1 in mice impairs normal splicing and causes premature termination of Aars2, leading to defects in heart development and postnatal lethality. Similarly, mice with a deletion in Aars2 that mimics a disease-causing splicing lesion display heart developmental abnormalities, reminiscent of those in patients with infantile mitochondrial cardiomyopathy. Mechanistically, loss of Pcbp1 or Aars2 in the heart reduces oxidative phosphorylation, a hallmark of patients with AARS2 mutations. This reduction in mitochondrial-encoded proteome activates mitonuclear communication and the unfolded protein response pathway, thereby inducing a compensatory nuclear-encoded mitochondrial gene program. Our findings provide insights into the PCBP1−AARS2 regulatory axis in mitochondrial cardiomyopathy. Lu et al. report that PCBP1 safeguards AARS2 alternative splicing in the heart, and that loss of PCBP1 disrupts AARS2 splicing, leading to infantile mitochondrial cardiomyopathy. Loss of cardiac PCBP1 or AARS2 impairs oxidative phosphorylation and activates mitonuclear signaling and the unfolded protein response pathway.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 4","pages":"328-350"},"PeriodicalIF":10.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-026-00798-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721043","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

Three-dimensional visualization of arrhythmogenic substrate in mouse hearts using panoramic optical mapping and micro-computed tomography. 利用全景光学成像和微计算机断层扫描对小鼠心脏内致心律失常底物的三维可视化。

IF 10.8

Nature cardiovascular research Pub Date : 2026-04-20 DOI: 10.1038/s44161-026-00803-9

Lea Melki, Uma Mahesh R Avula, Pavithran Guttipatti, Ruiping Ji, Najla Saadallah, Muhammad Shaher Yar, Jonah A Majumder, Albert Fang, Amar Desai, Naoko Yamaguchi, David S Park, Ashwin Viswanathan, Karen Conboy, Brian Gill, Christine P Hendon, Elaine Y Wan

{"title":"Three-dimensional visualization of arrhythmogenic substrate in mouse hearts using panoramic optical mapping and micro-computed tomography.","authors":"Lea Melki, Uma Mahesh R Avula, Pavithran Guttipatti, Ruiping Ji, Najla Saadallah, Muhammad Shaher Yar, Jonah A Majumder, Albert Fang, Amar Desai, Naoko Yamaguchi, David S Park, Ashwin Viswanathan, Karen Conboy, Brian Gill, Christine P Hendon, Elaine Y Wan","doi":"10.1038/s44161-026-00803-9","DOIUrl":"10.1038/s44161-026-00803-9","url":null,"abstract":"Electrical and structural remodeling of the heart can contribute to the development of cardiac arrhythmias. Ex vivo optical mapping has been used to visualize cardiac electrophysiological properties, activation and phase maps to further elucidate the mechanisms of atrial fibrillation and ventricular fibrillation initiation and persistence. Here we show an epicardial three-dimensional panoramic optical mapping tool integrated with micro-computed tomography automatically segmented with a deep learning model relying on a convolutional neural network to provide structural and electrical activation information in a single three-dimensional volume of a mouse heart. This technique allows for the acquisition and analysis of electrical activity of the entire epicardial surface with submillimeter spatial resolution and a temporal resolution of 1 ms. We establish the use of this method in transgenic mouse hearts with spontaneous atrial fibrillation and ventricular fibrillation, and mouse surgical models of myocardial infarction and left ventricular hypertrophy.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147730874","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

How RNA splicing decisions shape and break the developing heart RNA剪接决定如何塑造和破坏发育中的心脏

IF 10.8

Nature cardiovascular research Pub Date : 2026-04-20 DOI: 10.1038/s44161-026-00801-x

Rachel L. DeLancey, Sunil K. Verma, Muge N. Kuyumcu-Martinez

引用次数: 0