Nature cardiovascular research最新文献_第3页

RNF20-mediated transcriptional pausing and VEGFA splicing orchestrate vessel growth RNF20 介导的转录暂停和 VEGFA 剪接协调了血管的生长。

IF 9.4

Nature cardiovascular research Pub Date : 2024-09-25 DOI: 10.1038/s44161-024-00546-5

Nalan Tetik-Elsherbiny, Adel Elsherbiny, Aadhyaa Setya, Johannes Gahn, Yongqin Tang, Purnima Gupta, Yanliang Dou, Heike Serke, Thomas Wieland, Alexandre Dubrac, Joerg Heineke, Michael Potente, Julio Cordero, Roxana Ola, Gergana Dobreva

{"title":"RNF20-mediated transcriptional pausing and VEGFA splicing orchestrate vessel growth","authors":"Nalan Tetik-Elsherbiny, Adel Elsherbiny, Aadhyaa Setya, Johannes Gahn, Yongqin Tang, Purnima Gupta, Yanliang Dou, Heike Serke, Thomas Wieland, Alexandre Dubrac, Joerg Heineke, Michael Potente, Julio Cordero, Roxana Ola, Gergana Dobreva","doi":"10.1038/s44161-024-00546-5","DOIUrl":"10.1038/s44161-024-00546-5","url":null,"abstract":"Signal-responsive gene expression is essential for vascular development, yet the mechanisms integrating signaling inputs with transcriptional activities are largely unknown. Here we show that RNF20, the primary E3 ubiquitin ligase for histone H2B, plays a multifaceted role in sprouting angiogenesis. RNF20 mediates RNA polymerase (Pol II) promoter-proximal pausing at genes highly paused in endothelial cells, involved in VEGFA signaling, stress response, cell cycle control and mRNA splicing. It also orchestrates large-scale mRNA processing events that alter the bioavailability and function of critical pro-angiogenic factors, such as VEGFA. Mechanistically, RNF20 restricts ERG-dependent Pol II pause release at highly paused genes while binding to Notch1 to promote H2B monoubiquitination at Notch target genes and Notch-dependent gene expression. This balance is crucial, as loss of Rnf20 leads to uncontrolled tip cell specification. Our findings highlight the pivotal role of RNF20 in regulating VEGF–Notch signaling circuits during vessel growth, underscoring its potential for therapeutic modulation of angiogenesis. Tetik-Elsherbiny et al. demonstrate that the E3 ubiquitin ligase RNF20 mediates RNA polymerase II promoter-proximal pausing and alternative splicing, regulating the bioavailability and signaling of pro-angiogenic factors and angiogenesis.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 10","pages":"1199-1216"},"PeriodicalIF":9.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00546-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333948","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

Measured and genetically predicted protein levels and cardiovascular diseases in UK Biobank and China Kadoorie Biobank 英国生物库和中国嘉道理生物库中测量和基因预测的蛋白质水平与心血管疾病。

IF 9.4

Nature cardiovascular research Pub Date : 2024-09-25 DOI: 10.1038/s44161-024-00545-6

Lars Lind, Mohsen Mazidi, Robert Clarke, Derrick A. Bennett, Rui Zheng

{"title":"Measured and genetically predicted protein levels and cardiovascular diseases in UK Biobank and China Kadoorie Biobank","authors":"Lars Lind, Mohsen Mazidi, Robert Clarke, Derrick A. Bennett, Rui Zheng","doi":"10.1038/s44161-024-00545-6","DOIUrl":"10.1038/s44161-024-00545-6","url":null,"abstract":"Several large-scale studies have measured plasma levels of the proteome in individuals with cardiovascular diseases (CVDs)1–7. However, since the majority of such proteins are interrelated2, it is difficult for observational studies to distinguish which proteins are likely to be of etiological relevance. Here we evaluate whether plasma levels of 2,919 proteins measured in 52,164 UK Biobank participants are associated with incident myocardial infarction, ischemic stroke or heart failure. Of those proteins, 126 were associated with all three CVD outcomes and 118 were associated with at least one CVD in the China Kadoorie Biobank. Mendelian randomization and colocalization analyses indicated that genetically determined levels of 47 and 18 proteins, respectively, were associated with CVDs, including FGF5, PROCR and FURIN. While the majority of protein–CVD observational associations were noncausal, these three proteins showed evidence to support potential causality and are therefore promising targets for drug treatment for CVD outcomes. Lind et al. investigate the causal relationship between plasma proteins and cardiovascular disease outcomes in patients of European and Chinese descent, identifying FGF5, PROCR and FURIN as promising targets for the development of new drugs.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 10","pages":"1189-1198"},"PeriodicalIF":9.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00545-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333947","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

Evolution of translational control and the emergence of genes and open reading frames in human and non-human primate hearts 翻译控制的进化以及人类和非人灵长类动物心脏中基因和开放阅读框的出现。

IF 9.4

Nature cardiovascular research Pub Date : 2024-09-24 DOI: 10.1038/s44161-024-00544-7

Jorge Ruiz-Orera, Duncan C. Miller, Johannes Greiner, Carolin Genehr, Aliki Grammatikaki, Susanne Blachut, Jeanne Mbebi, Giannino Patone, Anna Myronova, Eleonora Adami, Nikita Dewani, Ning Liang, Oliver Hummel, Michael B. Muecke, Thomas B. Hildebrandt, Guido Fritsch, Lisa Schrade, Wolfram H. Zimmermann, Ivanela Kondova, Sebastian Diecke, Sebastiaan van Heesch, Norbert Hübner

{"title":"Evolution of translational control and the emergence of genes and open reading frames in human and non-human primate hearts","authors":"Jorge Ruiz-Orera, Duncan C. Miller, Johannes Greiner, Carolin Genehr, Aliki Grammatikaki, Susanne Blachut, Jeanne Mbebi, Giannino Patone, Anna Myronova, Eleonora Adami, Nikita Dewani, Ning Liang, Oliver Hummel, Michael B. Muecke, Thomas B. Hildebrandt, Guido Fritsch, Lisa Schrade, Wolfram H. Zimmermann, Ivanela Kondova, Sebastian Diecke, Sebastiaan van Heesch, Norbert Hübner","doi":"10.1038/s44161-024-00544-7","DOIUrl":"10.1038/s44161-024-00544-7","url":null,"abstract":"Evolutionary innovations can be driven by changes in the rates of RNA translation and the emergence of new genes and small open reading frames (sORFs). In this study, we characterized the transcriptional and translational landscape of the hearts of four primate and two rodent species through integrative ribosome and transcriptomic profiling, including adult left ventricle tissues and induced pluripotent stem cell-derived cardiomyocyte cell cultures. We show here that the translational efficiencies of subunits of the mitochondrial oxidative phosphorylation chain complexes IV and V evolved rapidly across mammalian evolution. Moreover, we discovered hundreds of species-specific and lineage-specific genomic innovations that emerged during primate evolution in the heart, including 551 genes, 504 sORFs and 76 evolutionarily conserved genes displaying human-specific cardiac-enriched expression. Overall, our work describes the evolutionary processes and mechanisms that have shaped cardiac transcription and translation in recent primate evolution and sheds light on how these can contribute to cardiac development and disease. Ruiz-Orera et al. used comparative transcriptomics and translatomics to analyze the cardiac evolution in primates and discovered species-specific and lineage-specific genomic innovations that might contribute to cardiac development and disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 10","pages":"1217-1235"},"PeriodicalIF":9.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00544-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333946","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

Cardiac NAD+ depletion in mice promotes hypertrophic cardiomyopathy and arrhythmias prior to impaired bioenergetics 小鼠心脏的 NAD+ 缺乏会在生物能受损之前导致肥厚型心肌病和心律失常。

IF 9.4

Nature cardiovascular research Pub Date : 2024-09-18 DOI: 10.1038/s44161-024-00542-9

Khanh V. Doan, Timothy S. Luongo, Thato T. Ts’olo, Won Dong Lee, David W. Frederick, Sarmistha Mukherjee, Gabriel K. Adzika, Caroline E. Perry, Ryan B. Gaspar, Nicole Walker, Megan C. Blair, Nicole Bye, James G. Davis, Corey D. Holman, Qingwei Chu, Lin Wang, Joshua D. Rabinowitz, Daniel P. Kelly, Thomas P. Cappola, Kenneth B. Margulies, Joseph A. Baur

{"title":"Cardiac NAD+ depletion in mice promotes hypertrophic cardiomyopathy and arrhythmias prior to impaired bioenergetics","authors":"Khanh V. Doan, Timothy S. Luongo, Thato T. Ts’olo, Won Dong Lee, David W. Frederick, Sarmistha Mukherjee, Gabriel K. Adzika, Caroline E. Perry, Ryan B. Gaspar, Nicole Walker, Megan C. Blair, Nicole Bye, James G. Davis, Corey D. Holman, Qingwei Chu, Lin Wang, Joshua D. Rabinowitz, Daniel P. Kelly, Thomas P. Cappola, Kenneth B. Margulies, Joseph A. Baur","doi":"10.1038/s44161-024-00542-9","DOIUrl":"10.1038/s44161-024-00542-9","url":null,"abstract":"Nicotinamide adenine dinucleotide (NAD+) is an essential co-factor in metabolic reactions and co-substrate for signaling enzymes. Failing human hearts display decreased expression of the major NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (Nampt) and lower NAD+ levels, and supplementation with NAD+ precursors is protective in preclinical models. Here we show that Nampt loss in adult cardiomyocytes caused depletion of NAD+ along with marked metabolic derangements, hypertrophic remodeling and sudden cardiac deaths, despite unchanged ejection fraction, endurance and mitochondrial respiratory capacity. These effects were directly attributable to NAD+ loss as all were ameliorated by restoring cardiac NAD+ levels with the NAD+ precursor nicotinamide riboside (NR). Electrocardiograms revealed that loss of myocardial Nampt caused a shortening of QT intervals with spontaneous lethal arrhythmias causing sudden cardiac death. Thus, changes in NAD+ concentration can have a profound influence on cardiac physiology even at levels sufficient to maintain energetics. Doan et al. show that loss of cardiac NAD+ is sufficient to drive metabolic derangements, hypertrophic remodeling and lethal arrhythmias in adult mouse hearts, despite maintenance of ejection fraction and bioenergetics.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 10","pages":"1236-1248"},"PeriodicalIF":9.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247373","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

Success in heart regeneration depends on endocardial innate immune signaling 心脏再生的成功取决于心内膜先天性免疫信号的传递

IF 9.4

Nature cardiovascular research Pub Date : 2024-09-13 DOI: 10.1038/s44161-024-00539-4

Kazu Kikuchi

引用次数: 0

Identifying a gene-regulatory network that drives fibromuscular dysplasia 确定驱动纤维肌发育不良的基因调控网络

IF 9.4

Nature cardiovascular research Pub Date : 2024-09-13 DOI: 10.1038/s44161-024-00534-9

引用次数: 0

Integrative gene regulatory network analysis discloses key driver genes of fibromuscular dysplasia 整合基因调控网络分析揭示纤维肌发育不良症的关键驱动基因

IF 9.4

Nature cardiovascular research Pub Date : 2024-09-13 DOI: 10.1038/s44161-024-00533-w

Valentina d’Escamard, Daniella Kadian-Dodov, Lijiang Ma, Sizhao Lu, Annette King, Yang Xu, Shouneng Peng, Bhargravi V′Gangula, Yu Zhou, Allison Thomas, Katherine C. Michelis, Emir Bander, Rihab Bouchareb, Adrien Georges, Aya Nomura-Kitabayashi, Robert J. Wiener, Kevin D. Costa, Elena Chepurko, Vadim Chepurko, Marika Fava, Temo Barwari, Anelechi Anyanwu, Farzan Filsoufi, Sander Florman, Nabila Bouatia-Naji, Lukas E. Schmidt, Manuel Mayr, Michael G. Katz, Ke Hao, Mary C. M. Weiser-Evans, Johan L. M. Björkegren, Jeffrey W. Olin, Jason C. Kovacic

{"title":"Integrative gene regulatory network analysis discloses key driver genes of fibromuscular dysplasia","authors":"Valentina d’Escamard, Daniella Kadian-Dodov, Lijiang Ma, Sizhao Lu, Annette King, Yang Xu, Shouneng Peng, Bhargravi V′Gangula, Yu Zhou, Allison Thomas, Katherine C. Michelis, Emir Bander, Rihab Bouchareb, Adrien Georges, Aya Nomura-Kitabayashi, Robert J. Wiener, Kevin D. Costa, Elena Chepurko, Vadim Chepurko, Marika Fava, Temo Barwari, Anelechi Anyanwu, Farzan Filsoufi, Sander Florman, Nabila Bouatia-Naji, Lukas E. Schmidt, Manuel Mayr, Michael G. Katz, Ke Hao, Mary C. M. Weiser-Evans, Johan L. M. Björkegren, Jeffrey W. Olin, Jason C. Kovacic","doi":"10.1038/s44161-024-00533-w","DOIUrl":"10.1038/s44161-024-00533-w","url":null,"abstract":"Fibromuscular dysplasia (FMD) is a poorly understood disease affecting 3–5% of adult females. The pathobiology of FMD involves arterial lesions of stenosis, dissection, tortuosity, dilation and aneurysm, which can lead to hypertension, stroke, myocardial infarction and even death. Currently, there are no animal models for FMD and few insights as to its pathobiology. In this study, by integrating DNA genotype and RNA sequence data from primary fibroblasts of 83 patients with FMD and 71 matched healthy controls, we inferred 18 gene regulatory co-expression networks, four of which were found to act together as an FMD-associated supernetwork in the arterial wall. After in vivo perturbation of this co-expression supernetwork by selective knockout of a top network key driver, mice developed arterial dilation, a hallmark of FMD. Molecular studies indicated that this supernetwork governs multiple aspects of vascular cell physiology and functionality, including collagen/matrix production. These studies illuminate the complex causal mechanisms of FMD and suggest a potential therapeutic avenue for this challenging disease. By integrating DNA genotype and RNA sequencing data from human samples, d’Escamard et al. identify a gene regulatory co-expression supernetwork that plays an important role in fibromuscular dysplasia, a poorly understood disease affecting 3–5% of adult females.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 9","pages":"1098-1122"},"PeriodicalIF":9.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231142","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 innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration 先天性免疫调节因子 MyD88 可抑制斑马鱼心脏再生过程中的纤维化

IF 9.4

Nature cardiovascular research Pub Date : 2024-09-13 DOI: 10.1038/s44161-024-00538-5

Pinelopi Goumenaki, Stefan Günther, Khrievono Kikhi, Mario Looso, Rubén Marín-Juez, Didier Y. R. Stainier

{"title":"The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration","authors":"Pinelopi Goumenaki, Stefan Günther, Khrievono Kikhi, Mario Looso, Rubén Marín-Juez, Didier Y. R. Stainier","doi":"10.1038/s44161-024-00538-5","DOIUrl":"10.1038/s44161-024-00538-5","url":null,"abstract":"The innate immune response is triggered rapidly after injury and its spatiotemporal dynamics are critical for regeneration; however, many questions remain about its exact role. Here we show that MyD88, a key component of the innate immune response, controls not only the inflammatory but also the fibrotic response during zebrafish cardiac regeneration. We find in cryoinjured myd88−/− ventricles a significant reduction in neutrophil and macrophage numbers and the expansion of a collagen-rich endocardial population. Further analyses reveal compromised PI3K/AKT pathway activation in the myd88−/− endocardium and increased myofibroblasts and scarring. Notably, endothelial-specific overexpression of myd88 reverses these neutrophil, fibrotic and scarring phenotypes. Mechanistically, we identify the endocardial-derived chemokine gene cxcl18b as a target of the MyD88 signaling pathway, and using loss-of-function and gain-of-function tools, we show that it controls neutrophil recruitment. Altogether, these findings shed light on the pivotal role of MyD88 in modulating inflammation and fibrosis during tissue regeneration. Goumenaki et al. uncover that during zebrafish cardiac regeneration, MyD88 signaling promotes the inflammatory response to injury and attenuates the endocardial-mediated fibrotic response.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 9","pages":"1158-1176"},"PeriodicalIF":9.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00538-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231130","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

Publisher Correction: Participation of ventricular trabeculae in neonatal cardiac regeneration leads to ectopic recruitment of Purkinje-like cells 出版商更正：心室小梁参与新生儿心脏再生导致浦肯野样细胞异位招募

IF 9.4

Nature cardiovascular research Pub Date : 2024-09-11 DOI: 10.1038/s44161-024-00548-3

Lucie Boulgakoff, Rachel Sturny, Veronika Olejnickova, David Sedmera, Robert G. Kelly, Lucile Miquerol

引用次数: 0

Macrophages and hematopoietic stem cells teach us that sharing is caring 巨噬细胞和造血干细胞告诉我们，分享就是关爱。

IF 9.4

Nature cardiovascular research Pub Date : 2024-09-10 DOI: 10.1038/s44161-024-00541-w

Gerburg Schwaerzer

引用次数: 0