Nature cardiovascular research最新文献_第10页

DNA-binding-deficient Hand2 dimerizes with Tcf3a to control zebrafish cardiogenesis dna结合缺陷Hand2与Tcf3a二聚体控制斑马鱼心脏发生。

IF 9.4

Nature cardiovascular research Pub Date : 2024-12-10 DOI: 10.1038/s44161-024-00589-8

引用次数: 0

PDGFRA is a conserved HAND2 effector during early cardiac development PDGFRA在早期心脏发育过程中是一个保守的HAND2效应因子。

IF 9.4

Nature cardiovascular research Pub Date : 2024-12-10 DOI: 10.1038/s44161-024-00574-1

Yanli Xu, Rupal Gehlot, Samuel J. Capon, Marga Albu, Jonas Gretz, Joshua Bloomekatz, Kenny Mattonet, Dubravka Vucicevic, Sweta Talyan, Khrievono Kikhi, Stefan Günther, Mario Looso, Beth A. Firulli, Miloslav Sanda, Anthony B. Firulli, Scott Allen Lacadie, Deborah Yelon, Didier Y. R. Stainier

{"title":"PDGFRA is a conserved HAND2 effector during early cardiac development","authors":"Yanli Xu, Rupal Gehlot, Samuel J. Capon, Marga Albu, Jonas Gretz, Joshua Bloomekatz, Kenny Mattonet, Dubravka Vucicevic, Sweta Talyan, Khrievono Kikhi, Stefan Günther, Mario Looso, Beth A. Firulli, Miloslav Sanda, Anthony B. Firulli, Scott Allen Lacadie, Deborah Yelon, Didier Y. R. Stainier","doi":"10.1038/s44161-024-00574-1","DOIUrl":"10.1038/s44161-024-00574-1","url":null,"abstract":"The basic helix–loop–helix transcription factor HAND2 has multiple roles during vertebrate organogenesis, including cardiogenesis. However, much remains to be uncovered about its mechanism of action. Here, we show the generation of several hand2 mutant alleles in zebrafish and demonstrate that dimerization-deficient mutants display the null phenotype but DNA-binding-deficient mutants do not. Rescue experiments with Hand2 variants using a newly identified hand2 enhancer confirmed these observations. To identify Hand2 effectors critical for cardiogenesis, we analyzed the transcriptomes of hand2 loss- and gain-of-function embryonic cardiomyocytes and tested the function of eight candidate genes in vivo; pdgfra was most effective in rescuing myocardial migration in hand2 mutants. Accordingly, we identified a putative Hand2-binding region in the zebrafish pdgfra locus that is important for its expression. In addition, Hand2 loss- and gain-of-function experiments in mouse embryonic stem cell-derived cardiac cells decreased and increased Pdgfra expression, respectively. Altogether, these results further our mechanistic understanding of HAND2 function during early cardiogenesis. Xu and colleagues show that the transcription factor Hand2 promotes pdgfra expression during early cardiogenesis and that it can do so independently of direct DNA binding by interacting with Tcf3.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 12","pages":"1531-1548"},"PeriodicalIF":9.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00574-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807170","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

Neutrophil extracellular traps worsen clotting and neuroinflammation in cavernomas 中性粒细胞胞外陷阱加重海绵状瘤的凝血和神经炎症。

IF 9.4

Nature cardiovascular research Pub Date : 2024-12-09 DOI: 10.1038/s44161-024-00584-z

引用次数: 0

Clonal hematopoiesis-related mutant ASXL1 promotes atherosclerosis in mice via dysregulated innate immunity 克隆造血相关突变ASXL1通过先天免疫失调促进小鼠动脉粥样硬化。

IF 9.4

Nature cardiovascular research Pub Date : 2024-12-09 DOI: 10.1038/s44161-024-00579-w

Naru Sato, Susumu Goyama, Yu-Hsuan Chang, Masashi Miyawaki, Takeshi Fujino, Shuhei Koide, Tamami Denda, Xiaoxiao Liu, Koji Ueda, Keita Yamamoto, Shuhei Asada, Reina Takeda, Taishi Yonezawa, Yosuke Tanaka, Hiroaki Honda, Yasunori Ota, Takuma Shibata, Motohiro Sekiya, Tomoya Isobe, Chrystelle Lamagna, Esteban Masuda, Atsushi Iwama, Hitoshi Shimano, Jun-ichiro Inoue, Kensuke Miyake, Toshio Kitamura

{"title":"Clonal hematopoiesis-related mutant ASXL1 promotes atherosclerosis in mice via dysregulated innate immunity","authors":"Naru Sato, Susumu Goyama, Yu-Hsuan Chang, Masashi Miyawaki, Takeshi Fujino, Shuhei Koide, Tamami Denda, Xiaoxiao Liu, Koji Ueda, Keita Yamamoto, Shuhei Asada, Reina Takeda, Taishi Yonezawa, Yosuke Tanaka, Hiroaki Honda, Yasunori Ota, Takuma Shibata, Motohiro Sekiya, Tomoya Isobe, Chrystelle Lamagna, Esteban Masuda, Atsushi Iwama, Hitoshi Shimano, Jun-ichiro Inoue, Kensuke Miyake, Toshio Kitamura","doi":"10.1038/s44161-024-00579-w","DOIUrl":"10.1038/s44161-024-00579-w","url":null,"abstract":"Certain somatic mutations provide a fitness advantage to hematopoietic stem cells and lead to clonal expansion of mutant blood cells, known as clonal hematopoiesis (CH). Among the most common CH mutations, ASXL1 mutations pose the highest risk for cardiovascular diseases (CVDs), yet the mechanisms by which they contribute to CVDs are unclear. Here we show that hematopoietic cells harboring C-terminally truncated ASXL1 mutant (ASXL1-MT) accelerate the development of atherosclerosis in Ldlr–/– mice. Transcriptome analyses of plaque cells showed that monocytes and macrophages expressing ASXL1-MT exhibit inflammatory signatures. Mechanistically, we demonstrate that wild-type ASXL1 has an unexpected non-epigenetic role by suppressing innate immune signaling through the inhibition of IRAK1–TAK1 interaction in the cytoplasm. This regulatory function is lost in ASXL1-MT, resulting in NF-κB activation. Inhibition of IRAK1/4 alleviated atherosclerosis driven by ASXL1-MT and decreased inflammatory monocytes. The present work provides a mechanistic and cellular explanation linking ASXL1 mutations, CH and CVDs. Somatic mutations in ASXL1 lead to clonal hematopoiesis, and Sato et al. elucidate the molecular mechanisms by which mutated ASXL1 in hematopoietic cells drives atherosclerosis in mice.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 12","pages":"1568-1583"},"PeriodicalIF":9.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802472","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

Chronic inflammation and vascular cell plasticity in atherosclerosis 动脉粥样硬化中的慢性炎症和血管细胞可塑性。

IF 9.4

Nature cardiovascular research Pub Date : 2024-12-09 DOI: 10.1038/s44161-024-00569-y

Alexander Lin, Joseph M. Miano, Edward A. Fisher, Ashish Misra

{"title":"Chronic inflammation and vascular cell plasticity in atherosclerosis","authors":"Alexander Lin, Joseph M. Miano, Edward A. Fisher, Ashish Misra","doi":"10.1038/s44161-024-00569-y","DOIUrl":"10.1038/s44161-024-00569-y","url":null,"abstract":"Vascular smooth muscle cells, endothelial cells and macrophages undergo phenotypic conversions throughout atherosclerosis progression, both as a consequence of chronic inflammation and as subsequent drivers of it. The inflammatory hypothesis of atherosclerosis has been catapulted to the forefront of cardiovascular research as clinical trials have shown that anti-inflammatory therapy reduces adverse cardiovascular events. However, no current therapies have been specifically designed to target the phenotype of plaque cells. Fate mapping has revealed that plaque cells convert to detrimental and beneficial cell phenotypes during atherosclerosis, with cumulative evidence highlighting that vascular cell plasticity is intimately linked with plaque inflammation, ultimately impacting lesion stability. Here we review vascular cell plasticity during atherosclerosis in the context of the chronic inflammatory plaque microenvironment. We highlight the need to better understand how plaque cells behave during therapeutic intervention. We then propose modulating plaque cell phenotype as an unexplored therapeutic paradigm in the clinical setting. Lin et al. review the phenotypic shifts in vascular smooth muscle and endothelial cells that both drive and result from the chronic inflammation characteristic of atherosclerosis progression. Their review provides insights into potential therapeutic strategies aimed at modulating plaque cell phenotypes to improve clinical outcomes.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 12","pages":"1408-1423"},"PeriodicalIF":9.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803939","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

Dynamic behavior and lineage plasticity of the pulmonary venous endothelium 肺静脉内皮的动态行为和谱系可塑性。

IF 9.4

Nature cardiovascular research Pub Date : 2024-12-09 DOI: 10.1038/s44161-024-00573-2

Joanna Wong, Gan Zhao, Stephanie Adams-Tzivelekidis, Hongbo Wen, Prashant Chandrasekaran, Sylvia N. Michki, Maria E. Gentile, Madeline Singh, Sara Kass-Gergi, Meryl Mendoza, Nicolas P. Holcomb, Xinyuan Li, Alan T. Tang, Nicholas M. Negretti, Jennifer M. S. Sucre, David B. Frank, Andrew E. Vaughan

{"title":"Dynamic behavior and lineage plasticity of the pulmonary venous endothelium","authors":"Joanna Wong, Gan Zhao, Stephanie Adams-Tzivelekidis, Hongbo Wen, Prashant Chandrasekaran, Sylvia N. Michki, Maria E. Gentile, Madeline Singh, Sara Kass-Gergi, Meryl Mendoza, Nicolas P. Holcomb, Xinyuan Li, Alan T. Tang, Nicholas M. Negretti, Jennifer M. S. Sucre, David B. Frank, Andrew E. Vaughan","doi":"10.1038/s44161-024-00573-2","DOIUrl":"10.1038/s44161-024-00573-2","url":null,"abstract":"Repair of the pulmonary vascular bed and the origin of new vasculature remain underexplored despite the critical necessity to meet oxygen demands after injury. Given their critical role in angiogenesis in other settings, we investigated the role of venous endothelial cells in endothelial regeneration after adult lung injury. Here we identified Slc6a2 as a marker of pulmonary venous endothelial cells and generated a venous-specific, inducible Cre mouse line. We observed that venous endothelial cells proliferate into the adjacent capillary bed upon influenza injury and hyperoxia injury. Imaging analysis demonstrated that venous endothelial cells proliferate and differentiate into general capillary and aerocyte capillary endothelial cells after infection, thus contributing to repair of the capillary plexus vital for gas exchange. Our studies thus establish that venous endothelial cells exhibit demonstrable progenitor capacity upon respiratory viral injury and sterile injury, contributing to repair of the alveolar capillary bed responsible for pulmonary function. Wong et al. identify Slc6a2 as a marker of pulmonary venous endothelial cells and demonstrate that these cells differentiate into capillary endothelial cells during vascular regeneration after lung injury.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 12","pages":"1584-1600"},"PeriodicalIF":9.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802500","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

Pharmacological blocking of neutrophil extracellular traps attenuates immunothrombosis and neuroinflammation in cerebral cavernous malformation 中性粒细胞胞外陷阱的药物阻断可减轻脑海绵状血管瘤的免疫血栓形成和神经炎症。

IF 9.4

Nature cardiovascular research Pub Date : 2024-12-04 DOI: 10.1038/s44161-024-00577-y

Favour C. Onyeogaziri, Ross Smith, Maximiliano Arce, Hua Huang, Iza Erzar, Charlotte Rorsman, Matteo Malinverno, Fabrizio Orsenigo, Veronica Sundell, Dinesh Fernando, Geoffrey Daniel, Mika Niemelä, Aki Laakso, Behnam Rezai Jahromi, Anna-Karin Olsson, Peetra U. Magnusson

{"title":"Pharmacological blocking of neutrophil extracellular traps attenuates immunothrombosis and neuroinflammation in cerebral cavernous malformation","authors":"Favour C. Onyeogaziri, Ross Smith, Maximiliano Arce, Hua Huang, Iza Erzar, Charlotte Rorsman, Matteo Malinverno, Fabrizio Orsenigo, Veronica Sundell, Dinesh Fernando, Geoffrey Daniel, Mika Niemelä, Aki Laakso, Behnam Rezai Jahromi, Anna-Karin Olsson, Peetra U. Magnusson","doi":"10.1038/s44161-024-00577-y","DOIUrl":"10.1038/s44161-024-00577-y","url":null,"abstract":"Cerebral cavernous malformation (CCM) is a neurovascular disease with symptoms such as strokes, hemorrhages and neurological deficits. With surgery being the only treatment strategy, understanding the molecular mechanisms of CCM is crucial in finding alternative therapeutic options for CCM. Neutrophil extracellular traps (NETs) were recently reported in CCM, and NETs were shown to have positive or negative effects in different disease contexts. In this study, we investigated the roles of NETs in CCM by pharmacologically inhibiting NET formation using Cl-amidine (a peptidyl arginine deiminase inhibitor). We show here that Cl-amidine treatment reduced lesion burden, coagulation and endothelial-to-mesenchymal transition. Furthermore, NETs promoted the activation of microglia and fibroblasts, leading to increased neuroinflammation and a chronic wound microenvironment in CCM. The inhibition of NET formation caused endothelial quiescence and promoted a healthier microenvironment. Our study suggests the inhibition of NETs as a potential therapeutic strategy in CCM. Onyeogaziri et al. show that the formation of neutrophil extracellular traps contributes to a chronic wound state in cerebral cavernous malformation, while inhibition of these traps with CI-amidine establishes a healthier microenvironment and promotes endothelial cell quiescence, suggesting use of CI-amidine as a potential therapeutic strategy.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 12","pages":"1549-1567"},"PeriodicalIF":9.4,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00577-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782025","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

New and future heart failure drugs 新的和未来的心力衰竭药物。

IF 9.4

Nature cardiovascular research Pub Date : 2024-12-04 DOI: 10.1038/s44161-024-00576-z

Leila Haghighat, Colette DeJong, John R. Teerlink

{"title":"New and future heart failure drugs","authors":"Leila Haghighat, Colette DeJong, John R. Teerlink","doi":"10.1038/s44161-024-00576-z","DOIUrl":"10.1038/s44161-024-00576-z","url":null,"abstract":"In the past decade, our understanding of heart failure pathophysiology has advanced significantly, resulting in the development of new medications such as angiotensin–neprilysin inhibitors, sodium–glucose cotransporter-2 inhibitors and oral soluble guanylate cyclase stimulators. Backed by positive findings from large randomized controlled trials, recommendations for their use were recently included in the 2022 AHA/ACC/HFSA guidelines and 2023 ESC guidelines for management of heart failure. Promising drugs for future heart failure treatment include agents that modulate the neurohormonal system, vasodilators, anti-inflammatory drugs, mitotropes, which improve deranged energy metabolism of the failing heart, and myotropes, which increase cardiac contractility by affecting cardiac sarcomere function. Here, we discuss these new and future heart failure drugs. We explain their mechanisms of action, critically evaluate their performance in clinical trials and summarize the clinical scenarios in which the latest guidelines recommend their use. This Review aims to offer clinicians and researchers a comprehensive overview of novel therapeutic classes in heart failure treatment. Haghighat et al. provide an overview of the newest advances in heart failure drugs, describing their mechanisms of action and performance in recent clinical trials, and discuss the most promising future directions for the field.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 12","pages":"1389-1407"},"PeriodicalIF":9.4,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781822","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

Immune checkpoint landscape of human atherosclerosis and influence of cardiometabolic factors 人动脉粥样硬化的免疫检查点景观及心脏代谢因素的影响。

IF 9.4

Nature cardiovascular research Pub Date : 2024-11-29 DOI: 10.1038/s44161-024-00563-4

José Gabriel Barcia Durán, Dayasagar Das, Michael Gildea, Letizia Amadori, Morgane Gourvest, Ravneet Kaur, Natalia Eberhardt, Panagiotis Smyrnis, Burak Cilhoroz, Swathy Sajja, Karishma Rahman, Dawn M. Fernandez, Peter Faries, Navneet Narula, Rami Vanguri, Ira J. Goldberg, Edward A. Fisher, Jeffrey S. Berger, Kathryn J. Moore, Chiara Giannarelli

{"title":"Immune checkpoint landscape of human atherosclerosis and influence of cardiometabolic factors","authors":"José Gabriel Barcia Durán, Dayasagar Das, Michael Gildea, Letizia Amadori, Morgane Gourvest, Ravneet Kaur, Natalia Eberhardt, Panagiotis Smyrnis, Burak Cilhoroz, Swathy Sajja, Karishma Rahman, Dawn M. Fernandez, Peter Faries, Navneet Narula, Rami Vanguri, Ira J. Goldberg, Edward A. Fisher, Jeffrey S. Berger, Kathryn J. Moore, Chiara Giannarelli","doi":"10.1038/s44161-024-00563-4","DOIUrl":"10.1038/s44161-024-00563-4","url":null,"abstract":"Immune checkpoint inhibitor (ICI) therapies can increase the risk of cardiovascular events in survivors of cancer by worsening atherosclerosis. Here we map the expression of immune checkpoints (ICs) within human carotid and coronary atherosclerotic plaques, revealing a network of immune cell interactions that ICI treatments can unintentionally target in arteries. We identify a population of mature, regulatory CCR7+FSCN1+ dendritic cells, similar to those described in tumors, as a hub of IC-mediated signaling within plaques. Additionally, we show that type 2 diabetes and lipid-lowering therapies alter immune cell interactions through PD-1, CTLA4, LAG3 and other IC targets in clinical development, impacting plaque inflammation. This comprehensive map of the IC interactome in healthy and cardiometabolic disease states provides a framework for understanding the potential adverse and beneficial impacts of approved and investigational ICIs on atherosclerosis, setting the stage for designing ICI strategies that minimize cardiovascular disease risk in cancer survivors. Barcia Durán, Dayasagar, et al. map the expression of immune checkpoints in human atherosclerosis and examine the influence of lipid-lowering treatments and type 2 diabetes to understand how immune checkpoint inhibitors worsen cardiovascular risk in survivors of cancer.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 12","pages":"1482-1502"},"PeriodicalIF":9.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00563-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755801","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

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