Nature cardiovascular research最新文献_第7页

Unrestrained cancer immunity ignites atherosclerosis 不受抑制的癌症免疫会引发动脉粥样硬化。

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-29 DOI: 10.1038/s44161-024-00571-4

Jesse W. Williams, Esther Lutgens

引用次数: 0

Mouse and human macrophages and their roles in cardiovascular health and disease 小鼠和人类巨噬细胞及其在心血管健康和疾病中的作用。

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-27 DOI: 10.1038/s44161-024-00580-3

Alexandre Gallerand, Jichang Han, Stoyan Ivanov, Gwendalyn J. Randolph

{"title":"Mouse and human macrophages and their roles in cardiovascular health and disease","authors":"Alexandre Gallerand, Jichang Han, Stoyan Ivanov, Gwendalyn J. Randolph","doi":"10.1038/s44161-024-00580-3","DOIUrl":"10.1038/s44161-024-00580-3","url":null,"abstract":"The past 15 years have witnessed a leap in understanding the life cycle, gene expression profiles, origins and functions of mouse macrophages in many tissues, including macrophages of the artery wall and heart that have critical roles in cardiovascular health. Here, we review the phenotypical and functional diversity of macrophage populations in multiple organs and discuss the roles that proliferation, survival, and recruitment and replenishment from monocytes have in maintaining macrophages in homeostasis and inflammatory states such as atherosclerosis and myocardial infarction. We also introduce emerging data that better characterize the life cycle and phenotypic profiles of human macrophages. We discuss the similarities and differences between murine and human macrophages, raising the possibility that tissue-resident macrophages in humans may rely more on bone marrow-derived monocytes than in mouse. Gallerand et al. review the main human and murine macrophage populations, highlighting their phenotypic and functional diversity and how they contribute to cardiovascular health by regulating the inflammatory response.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 12","pages":"1424-1437"},"PeriodicalIF":9.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741713","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 tRNA methyltransferase Mettl1 governs ketogenesis through translational regulation and drives metabolic reprogramming in cardiomyocyte maturation tRNA甲基转移酶Mettl1通过翻译调节控制酮体生成，并在心肌细胞成熟过程中驱动代谢重编程。

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-25 DOI: 10.1038/s44161-024-00565-2

Tailai Du, Yanchuang Han, Hui Han, Ting Xu, Youchen Yan, Jialing Wu, Yan Li, Chen Liu, Xinxue Liao, Yugang Dong, Demeng Chen, Jingsong Ou, Shuibin Lin, Zhan-Peng Huang

{"title":"The tRNA methyltransferase Mettl1 governs ketogenesis through translational regulation and drives metabolic reprogramming in cardiomyocyte maturation","authors":"Tailai Du, Yanchuang Han, Hui Han, Ting Xu, Youchen Yan, Jialing Wu, Yan Li, Chen Liu, Xinxue Liao, Yugang Dong, Demeng Chen, Jingsong Ou, Shuibin Lin, Zhan-Peng Huang","doi":"10.1038/s44161-024-00565-2","DOIUrl":"10.1038/s44161-024-00565-2","url":null,"abstract":"After birth, the heart undergoes a shift in energy metabolism and cytoarchitecture to enhance efficient energy production and cardiac contraction, which is essential for postnatal development and growth. However, the precise mechanisms regulating this process remain elusive. Here we show that the RNA modification enzyme Mettl1 is a critical regulator of postnatal metabolic reprogramming and cardiomyocyte maturation in mice, primarily through its influence on the translation of the rate-limiting ketogenesis enzyme Hmgcs2. Our findings reveal that ketogenesis is vital for the postnatal transition of fuel from glucose to fatty acids in cardiomyocytes, achieved by modulating tricarboxylic acid cycle–related enzymatic activity via lysine β-hydroxybutyrylation protein modification. Loss of Mettl1 results in aberrant metabolic reprogramming and cardiomyocyte immaturity, leading to heart failure, although some clinical features can be rescued by β-hydroxybutyrate supplementation. Our study provides mechanistic insights into how Mettl1 regulates metabolic reprogramming in neonatal cardiomyocytes and highlights the importance of ketogenesis in cardiomyocyte maturation. Du et al. elucidate the mechanism by which Mettl1, a tRNA m7G methyltransferase, regulates cardiomyocyte maturation by influencing the translation of the rate-limiting ketogenesis enzyme Hmgcs2, thereby impacting cardiomyocyte fuel utilization.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 12","pages":"1438-1453"},"PeriodicalIF":9.4,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717934","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

tRNA methylation drives early postnatal cardiomyocyte maturation tRNA 甲基化驱动出生后早期心肌细胞成熟

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-25 DOI: 10.1038/s44161-024-00572-3

Pilar Ruiz-Lozano, Mark Mercola

引用次数: 0

Integrative proteomic analyses across common cardiac diseases yield mechanistic insights and enhanced prediction 对常见心脏疾病进行综合蛋白质组分析，有助于深入了解机理并加强预测。

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-21 DOI: 10.1038/s44161-024-00567-0

Art Schuermans, Ashley B. Pournamdari, Jiwoo Lee, Rohan Bhukar, Shriienidhie Ganesh, Nicholas Darosa, Aeron M. Small, Zhi Yu, Whitney Hornsby, Satoshi Koyama, Charles Kooperberg, Alexander P. Reiner, James L. Januzzi Jr., Michael C. Honigberg, Pradeep Natarajan

{"title":"Integrative proteomic analyses across common cardiac diseases yield mechanistic insights and enhanced prediction","authors":"Art Schuermans, Ashley B. Pournamdari, Jiwoo Lee, Rohan Bhukar, Shriienidhie Ganesh, Nicholas Darosa, Aeron M. Small, Zhi Yu, Whitney Hornsby, Satoshi Koyama, Charles Kooperberg, Alexander P. Reiner, James L. Januzzi Jr., Michael C. Honigberg, Pradeep Natarajan","doi":"10.1038/s44161-024-00567-0","DOIUrl":"10.1038/s44161-024-00567-0","url":null,"abstract":"Cardiac diseases represent common highly morbid conditions for which molecular mechanisms remain incompletely understood. Here we report the analysis of 1,459 protein measurements in 44,313 UK Biobank participants to characterize the circulating proteome associated with incident coronary artery disease, heart failure, atrial fibrillation and aortic stenosis. Multivariable-adjusted Cox regression identified 820 protein–disease associations—including 441 proteins—at Bonferroni-adjusted P < 8.6 × 10−6. Cis-Mendelian randomization suggested causal roles aligning with epidemiological findings for 4% of proteins identified in primary analyses, prioritizing therapeutic targets across cardiac diseases (for example, spondin-1 for atrial fibrillation and the Kunitz-type protease inhibitor 1 for coronary artery disease). Interaction analyses identified seven protein–disease associations that differed Bonferroni-significantly by sex. Models incorporating proteomic data (versus clinical risk factors alone) improved prediction for coronary artery disease, heart failure and atrial fibrillation. These results lay a foundation for future investigations to uncover disease mechanisms and assess the utility of protein-based prevention strategies for cardiac diseases. Schuermans et al. identify a causal relationship between the circulating proteins spondin-1 and atrial fibrillation and SPINT1 and coronary artery disease and show that adding proteomic data improves clinical risk factor-based cardiovascular risk prediction.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 12","pages":"1516-1530"},"PeriodicalIF":9.4,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00567-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689890","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 and phenotypic architecture of human myocardial trabeculation 人类心肌小梁的遗传和表型结构。

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-20 DOI: 10.1038/s44161-024-00564-3

Kathryn A. McGurk, Mengyun Qiao, Sean L. Zheng, Arunashis Sau, Albert Henry, Antonio Luiz P. Ribeiro, Antônio H. Ribeiro, Fu Siong Ng, R. Thomas Lumbers, Wenjia Bai, James S. Ware, Declan P. O’Regan

{"title":"Genetic and phenotypic architecture of human myocardial trabeculation","authors":"Kathryn A. McGurk, Mengyun Qiao, Sean L. Zheng, Arunashis Sau, Albert Henry, Antonio Luiz P. Ribeiro, Antônio H. Ribeiro, Fu Siong Ng, R. Thomas Lumbers, Wenjia Bai, James S. Ware, Declan P. O’Regan","doi":"10.1038/s44161-024-00564-3","DOIUrl":"10.1038/s44161-024-00564-3","url":null,"abstract":"Cardiac trabeculae form a network of muscular strands that line the inner surfaces of the heart. Their development depends on multiscale morphogenetic processes and, while highly conserved across vertebrate evolution, their role in the pathophysiology of the mature heart is not fully understood. Here we report variant associations across the allele frequency spectrum for trabecular morphology in 47,803 participants of the UK Biobank using fractal dimension analysis of cardiac imaging. We identified an association between trabeculation and rare variants in 56 genes that regulate myocardial contractility and ventricular development. Genome-wide association studies identified 68 loci in pathways that regulate sarcomeric function, differentiation of the conduction system and cell fate determination. We found that trabeculation-associated variants were modifiers of cardiomyopathy phenotypes with opposing effects in hypertrophic and dilated cardiomyopathy. Together, these data provide insights into mechanisms that regulate trabecular development and plasticity, and identify a potential role in modifying monogenic disease expression. The inner surface of the heart has a meshwork of muscles called trabeculae. McGurk et al. report the genetic regulation of these complex structures across common and rare variants, revealing pathways implicated in heart development and cell fate.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 12","pages":"1503-1515"},"PeriodicalIF":9.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00564-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683298","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

Intrinsic GATA4 expression sensitizes the aortic root to dilation in a Loeys–Dietz syndrome mouse model 在 Loeys-Dietz 综合征小鼠模型中，GATA4 的内在表达使主动脉根部对扩张敏感。

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-20 DOI: 10.1038/s44161-024-00562-5

Emily E. Bramel, Wendy A. Espinoza Camejo, Tyler J. Creamer, Leda Restrepo, Muzna Saqib, Rustam Bagirzadeh, Anthony Zeng, Jacob T. Mitchell, Genevieve L. Stein-O’Brien, Albert J. Pedroza, Michael P. Fischbein, Harry C. Dietz, Elena Gallo MacFarlane

{"title":"Intrinsic GATA4 expression sensitizes the aortic root to dilation in a Loeys–Dietz syndrome mouse model","authors":"Emily E. Bramel, Wendy A. Espinoza Camejo, Tyler J. Creamer, Leda Restrepo, Muzna Saqib, Rustam Bagirzadeh, Anthony Zeng, Jacob T. Mitchell, Genevieve L. Stein-O’Brien, Albert J. Pedroza, Michael P. Fischbein, Harry C. Dietz, Elena Gallo MacFarlane","doi":"10.1038/s44161-024-00562-5","DOIUrl":"10.1038/s44161-024-00562-5","url":null,"abstract":"Loeys–Dietz syndrome (LDS) is a connective tissue disorder caused by mutations that decrease transforming growth factor-β signaling. LDS-causing mutations increase the risk of aneurysm throughout the arterial tree, yet the aortic root is a site of heightened susceptibility. Here we investigate the heterogeneity of vascular smooth muscle cells (VSMCs) in the aorta of Tgfbr1M318R/+ LDS mice by single-cell transcriptomics to identify molecular determinants of this vulnerability. Reduced expression of components of the extracellular matrix–receptor apparatus and upregulation of stress and inflammatory pathways were observed in all LDS VSMCs. However, regardless of genotype, a subset of Gata4-expressing VSMCs predominantly located in the aortic root intrinsically displayed a less differentiated, proinflammatory profile. A similar population was also identified among aortic VSMCs in a human single-cell RNA sequencing dataset. Postnatal VSMC-specific Gata4 deletion reduced aortic root dilation in LDS mice, suggesting that this factor sensitizes the aortic root to the effects of impaired transforming growth factor-β signaling. Bramel et al. identify a population of GATA4+ vascular smooth muscle cells enriched in the human and mouse aortic root that is intrinsically more susceptible to Loeys–Dietz-syndrome-causing mutations and demonstrate that postnatal deletion of Gata4 in vascular smooth muscle cells reduces aortic root dilation in a mouse model of Loeys–Dietz syndrome.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 12","pages":"1468-1481"},"PeriodicalIF":9.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00562-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683373","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

Glutamine–glutamate imbalance in the pathogenesis of cardiovascular disease 心血管疾病发病机制中的谷氨酰胺-谷氨酸失衡。

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-19 DOI: 10.1038/s44161-024-00575-0

Ziyang Liu, Ali Ajam, Jun Huang, Yu-Sheng Yeh, Babak Razani

引用次数: 0

GLS2 links glutamine metabolism and atherosclerosis by remodeling artery walls GLS2 通过重塑动脉壁将谷氨酰胺代谢与动脉粥样硬化联系起来。

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-19 DOI: 10.1038/s44161-024-00566-1

Florent Murcy, Coraline Borowczyk, Samuel Gourion-Arsiquaud, Stéphanie Torrino, Nessrine Ouahrouche, Thibault Barouillet, Sébastien Dussaud, Marie Couralet, Nathalie Vaillant, Johanna Merlin, Alexandre Berquand, Minna U. Kaikkonen, Robyn L. McClelland, William Tressel, James Stein, Edward B. Thorp, Thomas Bertero, Pascal Barbry, Béatrice Bailly-Maitre, Emmanuel L. Gautier, Minna K. Karjalainen, Johannes Kettunen, Laurent Duca, Steven Shea, Laurent Yvan-Charvet

{"title":"GLS2 links glutamine metabolism and atherosclerosis by remodeling artery walls","authors":"Florent Murcy, Coraline Borowczyk, Samuel Gourion-Arsiquaud, Stéphanie Torrino, Nessrine Ouahrouche, Thibault Barouillet, Sébastien Dussaud, Marie Couralet, Nathalie Vaillant, Johanna Merlin, Alexandre Berquand, Minna U. Kaikkonen, Robyn L. McClelland, William Tressel, James Stein, Edward B. Thorp, Thomas Bertero, Pascal Barbry, Béatrice Bailly-Maitre, Emmanuel L. Gautier, Minna K. Karjalainen, Johannes Kettunen, Laurent Duca, Steven Shea, Laurent Yvan-Charvet","doi":"10.1038/s44161-024-00566-1","DOIUrl":"10.1038/s44161-024-00566-1","url":null,"abstract":"Metabolic dysregulation, including perturbed glutamine–glutamate homeostasis, is common among patients with cardiovascular diseases, but the underlying mechanisms remain largely unknown. Using the human MESA cohort, here we show that plasma glutamine–glutamate ratio is an independent risk factor for carotid plaque progression. Mice deficient in glutaminase-2 (Gls2), the enzyme that mediates hepatic glutaminolysis, developed accelerated atherosclerosis and susceptibility to catastrophic cardiac events, while Gls2 overexpression partially protected from disease progression. High-throughput transcriptional profiling and high-resolution structural biology imaging of aortas showed that Gls2 deficiency perturbed extracellular matrix composition and increased vessel stiffness. This results from an imbalance of glutamine- and glutamate-dependent cross-linked proteins within atherosclerotic lesions and cellular remodeling of plaques. Thus, hepatic glutaminolysis functions as a potent regulator of glutamine homeostasis, which affects the aortic wall structure during atherosclerotic plaque progression. Murcy et al. show that increasing the plasma glutamine-to-glutamate ratio in atherosclerosis can distally reprogram transcriptional and post-transcriptional remodeling of the aorta by GLS2-dependent hepatic glutaminolysis.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 12","pages":"1454-1467"},"PeriodicalIF":9.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677982","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

Cardiac regeneration leads to altered Purkinje fiber network and ventricular conduction 心脏再生导致浦肯野纤维网和心室传导发生改变

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-12 DOI: 10.1038/s44161-024-00549-2

引用次数: 0