Nature cardiovascular research最新文献

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, 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, 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.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689890","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

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":"https://doi.org/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.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683298","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

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":"https://doi.org/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.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683373","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

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":"https://doi.org/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.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"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

Klf9 is essential for cardiac mitochondrial homeostasis Klf9 对心脏线粒体的稳态至关重要

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-08 DOI: 10.1038/s44161-024-00561-6

Lei Zhang, Menglin Zhang, Jinlong Huang, Jincan Huang, Yujie Zhang, Yinliang Zhang, Houzao Chen, Cuizhe Wang, Xiangwen Xi, Heng Fan, Jikui Wang, Dingsheng Jiang, Jinwei Tian, Jun Zhang, Yongsheng Chang

{"title":"Klf9 is essential for cardiac mitochondrial homeostasis","authors":"Lei Zhang, Menglin Zhang, Jinlong Huang, Jincan Huang, Yujie Zhang, Yinliang Zhang, Houzao Chen, Cuizhe Wang, Xiangwen Xi, Heng Fan, Jikui Wang, Dingsheng Jiang, Jinwei Tian, Jun Zhang, Yongsheng Chang","doi":"10.1038/s44161-024-00561-6","DOIUrl":"10.1038/s44161-024-00561-6","url":null,"abstract":"Mitochondrial dynamics and mitophagy are intimately linked physiological processes that are essential for cardiac homeostasis. Here we show that cardiac Krüppel-like factor 9 (Klf9) is dysregulated in human and rodent cardiomyopathy. Both global and cardiac-specific Klf9-deficient mice displayed hypertrophic cardiomyopathy. Klf9 knockout led to mitochondrial disarray and fragmentation, impairing mitochondrial respiratory function in cardiomyocytes. Furthermore, cardiac Klf9 deficiency inhibited mitophagy, thereby causing accumulation of dysfunctional mitochondria and acceleration of heart failure in response to angiotensin II treatment. In contrast, cardiac-specific Klf9 transgene improved cardiac systolic function. Mechanistically, Klf9 knockout decreased the expression of PGC-1α and its target genes involved in mitochondrial energy metabolism. Moreover, Klf9 controlled the expression of Mfn2, thereby regulating mitochondrial dynamics and mitophagy. Finally, adeno-associated virus–mediated Mfn2 rescue in Klf9-CKO hearts improved cardiac mitochondrial and systolic function. Thus, Klf9 integrates cardiac energy metabolism, mitochondrial dynamics and mitophagy. Modulating Klf9 activity may have therapeutic potential in the treatment of heart failure. L. Zhang, M. Zhang, Huang et al. show that Klf9 regulated PGC-1α and Mfn2 expression, contributing to mitochondrial energy metabolism and dynamic regulation, promoting mitophagy, improving cardiac function and revealing a potential therapeutic target.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 11","pages":"1318-1336"},"PeriodicalIF":9.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142600842","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

Influence of sleep on physiological systems in atherosclerosis 睡眠对动脉粥样硬化生理系统的影响

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-08 DOI: 10.1038/s44161-024-00560-7

Máté G. Kiss, Oren Cohen, Cameron S. McAlpine, Filip K. Swirski

引用次数: 0

Concealed cardiomyopathy as an emerging cause of sudden cardiac arrest and sudden cardiac death 隐匿性心肌病是导致心脏骤停和心脏性猝死的一个新原因。

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-01 DOI: 10.1038/s44161-024-00558-1

Julia C. Isbister, Rafik Tadros, Hariharan Raju, Christopher Semsarian

{"title":"Concealed cardiomyopathy as an emerging cause of sudden cardiac arrest and sudden cardiac death","authors":"Julia C. Isbister, Rafik Tadros, Hariharan Raju, Christopher Semsarian","doi":"10.1038/s44161-024-00558-1","DOIUrl":"10.1038/s44161-024-00558-1","url":null,"abstract":"The inherited cardiomyopathies exhibit a broad spectrum of disease, with some patients remaining asymptomatic throughout life, while, for others, the first symptom of disease is sudden cardiac death at a young age. The risk of malignant ventricular arrhythmia in these conditions has traditionally been linked to the degree of structural myocardial abnormalities and functional impairment. However, recent advances in genetic testing and knowledge of the genetic basis of the diseases have led to the identification of concealed cardiomyopathy, in which sudden cardiac arrest or sudden cardiac death occurs in the absence of observable clinical features of cardiomyopathy, with a diagnosis being made only after the identification of a causative genetic variant. Increased awareness of concealed cardiomyopathy, a better understanding of mechanisms of arrhythmia and identification of risk modulators will be vital to improve care for families with concealed cardiomyopathy. Isbister et al. review the recent advances in understanding the genetic basis of the diseases that have led to the identification of concealed cardiomyopathy, where sudden cardiac arrest or death occurs even in the absence of observable clinical features of cardiomyopathy.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 11","pages":"1274-1283"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564837","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

CDK6-mediated endothelial cell cycle acceleration drives arteriovenous malformations in hereditary hemorrhagic telangiectasia CDK6介导的内皮细胞周期加速驱动遗传性出血性毛细血管扩张症中的动静脉畸形。

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-01 DOI: 10.1038/s44161-024-00550-9

Sajeth Dinakaran, Sima Qutaina, Haitian Zhao, Yuefeng Tang, Zhimin Wang, Santiago Ruiz, Aya Nomura-Kitabayashi, Christine N. Metz, Helen M. Arthur, Stryder M. Meadows, Lionel Blanc, Marie E. Faughnan, Philippe Marambaud

{"title":"CDK6-mediated endothelial cell cycle acceleration drives arteriovenous malformations in hereditary hemorrhagic telangiectasia","authors":"Sajeth Dinakaran, Sima Qutaina, Haitian Zhao, Yuefeng Tang, Zhimin Wang, Santiago Ruiz, Aya Nomura-Kitabayashi, Christine N. Metz, Helen M. Arthur, Stryder M. Meadows, Lionel Blanc, Marie E. Faughnan, Philippe Marambaud","doi":"10.1038/s44161-024-00550-9","DOIUrl":"10.1038/s44161-024-00550-9","url":null,"abstract":"Increased endothelial cell proliferation is a hallmark of arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT). Here, we report a cyclin-dependent kinase 6 (CDK6)-driven mechanism of cell cycle deregulation involved in endothelial cell proliferation and HHT pathology. Specifically, endothelial cells from the livers of HHT mice bypassed the G1/S checkpoint and progressed through the cell cycle at an accelerated pace. Phosphorylated retinoblastoma (pRB1)—a marker of G1/S transition through the restriction point—accumulated in endothelial cells from retinal AVMs of HHT mice and endothelial cells from skin telangiectasia samples from HHT patients. Mechanistically, inhibition of activin receptor-like kinase 1 signaling increased key restriction point mediators, and treatment with the CDK4/6 inhibitors palbociclib or ribociclib blocked increases in pRB1 and retinal AVMs in HHT mice. Palbociclib also improved vascular pathology in the brain and liver, and slowed cell cycle progression in endothelial cells and endothelial cell proliferation. Endothelial cell-specific deletion of CDK6 was sufficient to protect HHT mice from AVM pathology. Thus, clinically approved CDK4/6 inhibitors might have the potential to be repurposed for HHT. Dinakaran et al. show that arteriovenous malformations in hereditary hemorrhagic telangiectasia are caused by CDK6-mediated cell cycle acceleration in response to BMP9/BMP10 inhibition and that CDK4/6 inhibitors can prevent the development of the disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 11","pages":"1301-1317"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564775","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