Nature cardiovascular research最新文献

{"title":"Challenges and perspectives of heart repair with pluripotent stem cell-derived cardiomyocytes","authors":"Thomas Eschenhagen, Florian Weinberger","doi":"10.1038/s44161-024-00472-6","DOIUrl":"10.1038/s44161-024-00472-6","url":null,"abstract":"Here we aim at providing a concise but comprehensive overview of the perspectives and challenges of heart repair with pluripotent stem cell-derived cardiomyocytes. This Review comes at a time when consensus has been reached about the lack of relevant proliferative capacity of adult mammalian cardiomyocytes and the lack of new heart muscle formation with autologous cell sources. While alternatives to cell-based approaches will be shortly summarized, the focus lies on pluripotent stem cell-derived cardiomyocyte repair, which entered first clinical trials just 2 years ago. In the view of the authors, these early trials are important but have to be viewed as early proof-of-concept trials in humans that will hopefully provide first answers on feasibility, safety and the survival of allogeneic pluripotent stem cell-derived cardiomyocyte in the human heart. Better approaches have to be developed to make this approach clinically applicable. Eschenhagen and Weinberger provide a concise and comprehensive overview of the perspectives and challenges of heart repair with pluripotent stem cell-derived cardiomyocytes.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"515-524"},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140979626","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}

{"title":"The role of asparagine synthetase in cardiomyocyte dedifferentiation","authors":"Michelle Korda","doi":"10.1038/s44161-024-00481-5","DOIUrl":"10.1038/s44161-024-00481-5","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"495-495"},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140981838","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}

{"title":"Development and multinational validation of an algorithmic strategy for high Lp(a) screening","authors":"Arya Aminorroaya, Lovedeep S. Dhingra, Evangelos K. Oikonomou, Seyedmohammad Saadatagah, Phyllis Thangaraj, Sumukh Vasisht Shankar, Erica S. Spatz, Rohan Khera","doi":"10.1038/s44161-024-00469-1","DOIUrl":"10.1038/s44161-024-00469-1","url":null,"abstract":"Elevated lipoprotein (a) (Lp(a)) is associated with premature atherosclerotic cardiovascular disease. However, fewer than 0.5% of individuals undergo Lp(a) testing, limiting the evaluation and use of novel targeted therapeutics currently under development. Here we describe the development of a machine learning model for targeted screening for elevated Lp(a) (≥150 nmol l−1) in the UK Biobank (N = 456,815), the largest cohort with protocolized Lp(a) testing. We externally validated the model in 3 large cohort studies, ARIC (N = 14,484), CARDIA (N = 4,124) and MESA (N = 4,672). The model, Algorithmic Risk Inspection for Screening Elevated Lp(a) (ARISE), reduced the number needed to test to find one individual with elevated Lp(a) by up to 67.3%, based on the probability threshold, with consistent performance across external validation cohorts. ARISE could be used to optimize screening for elevated Lp(a) using commonly available clinical features, with the potential for its deployment in electronic health records to enhance the yield of Lp(a) testing in real-world settings. Elevated Lp(a) is an independent atherosclerosis risk factor that is not routinely measured in the general population. Aminorroaya et al. develop and validate a machine learning model, ARISE, that allows for the detection of elevated Lp(a) using commonly available clinical features from electronic records.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"558-566"},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140994209","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}

{"title":"Alcohol-mediated renal denervation is a safe and efficient treatment for uncontrolled hypertension","authors":"Gerburg Schwaerzer","doi":"10.1038/s44161-024-00476-2","DOIUrl":"10.1038/s44161-024-00476-2","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"493-493"},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140998377","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}

{"title":"Primitive macrophages induce sarcomeric maturation and functional enhancement of developing human cardiac microtissues via efferocytic pathways","authors":"Homaira Hamidzada, Simon Pascual-Gil, Qinghua Wu, Gregory M. Kent, Stéphane Massé, Crystal Kantores, Uros Kuzmanov, M. Juliana Gomez-Garcia, Naimeh Rafatian, Renée A. Gorman, Marianne Wauchop, Wenliang Chen, Shira Landau, Tasnia Subha, Michael H. Atkins, Yimu Zhao, Erika Beroncal, Ian Fernandes, Jared Nanthakumar, Shabana Vohra, Erika Y. Wang, Tamilla Valdman Sadikov, Babak Razani, Tracy L. McGaha, Ana C. Andreazza, Anthony Gramolini, Peter H. Backx, Kumaraswamy Nanthakumar, Michael A. Laflamme, Gordon Keller, Milica Radisic, Slava Epelman","doi":"10.1038/s44161-024-00471-7","DOIUrl":"10.1038/s44161-024-00471-7","url":null,"abstract":"Yolk sac macrophages are the first to seed the developing heart; however, owing to a lack of accessible tissue, there is no understanding of their roles in human heart development and function. In this study, we bridge this gap by differentiating human embryonic stem (hES) cells into primitive LYVE1+ macrophages (hESC-macrophages) that stably engraft within contractile cardiac microtissues composed of hESC-cardiomyocytes and fibroblasts. Engraftment induces a human fetal cardiac macrophage gene program enriched in efferocytic pathways. Functionally, hESC-macrophages trigger cardiomyocyte sarcomeric protein maturation, enhance contractile force and improve relaxation kinetics. Mechanistically, hESC-macrophages engage in phosphatidylserine-dependent ingestion of apoptotic cardiomyocyte cargo, which reduces microtissue stress, leading hESC-cardiomyocytes to more closely resemble early human fetal ventricular cardiomyocytes, both transcriptionally and metabolically. Inhibiting hESC-macrophage efferocytosis impairs sarcomeric protein maturation and reduces cardiac microtissue function. Together, macrophage-engineered human cardiac microtissues represent a considerably improved model for human heart development and reveal a major beneficial role for human primitive macrophages in enhancing early cardiac tissue function. Hamidzada et al. show that human pluripotent stem cell–derived macrophages are educated into a tissue-resident fate within human cardiac microtissues, enhancing its function via efferocytic ingestion of stressed cardiomyocyte cargo.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"567-593"},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141002294","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}

{"title":"Female sex is not a component of stroke risk in atrial fibrillation","authors":"Andrea Tavosanis","doi":"10.1038/s44161-024-00477-1","DOIUrl":"10.1038/s44161-024-00477-1","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"494-494"},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141016723","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}

{"title":"Mitochondrial calcium uniporter channel gatekeeping in cardiovascular disease","authors":"Tyler L. Stevens, Henry M. Cohen, Joanne F. Garbincius, John W. Elrod","doi":"10.1038/s44161-024-00463-7","DOIUrl":"10.1038/s44161-024-00463-7","url":null,"abstract":"The mitochondrial calcium (mCa2+) uniporter channel (mtCU) resides at the inner mitochondrial membrane and is required for Ca2+ to enter the mitochondrial matrix. The mtCU is essential for cellular function, as mCa2+ regulates metabolism, bioenergetics, signaling pathways and cell death. mCa2+ uptake is primarily regulated by the MICU family (MICU1, MICU2, MICU3), EF-hand-containing Ca2+-sensing proteins, which respond to cytosolic Ca2+ concentrations to modulate mtCU activity. Considering that mitochondrial function and Ca2+ signaling are ubiquitously disrupted in cardiovascular disease, mtCU function has been a hot area of investigation for the last decade. Here we provide an in-depth review of MICU-mediated regulation of mtCU structure and function, as well as potential mtCU-independent functions of these proteins. We detail their role in cardiac physiology and cardiovascular disease by highlighting the phenotypes of different mutant animal models, with an emphasis on therapeutic potential and targets of interest in this pathway. Stevens et al. review the current knowledge on the regulation of the mitochondrial calcium uniporter channel (mtCU) in cardiac physiology and disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"500-514"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141049151","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}

{"title":"Directions for promoting patency of arterial grafts","authors":"","doi":"10.1038/s44161-024-00466-4","DOIUrl":"10.1038/s44161-024-00466-4","url":null,"abstract":"By dissecting the cell composition and function of arterial grafts derived from the internal thoracic, radial and right gastroepiploic arteries, we identified factors that might promote patency rates of arterial grafts, including combating lipid deposition, disturbances in wall shear stress, smooth muscle cell proliferation, fibrosis and spasm.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"498-499"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069185","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}

{"title":"Strategies for arterial graft optimization at the single-cell level","authors":"Zhan Hu, Min Dai, Yuan Chang, Xiumeng Hua, Ningning Zhang, Xiao Chen, Yixuan Sheng, Zhenyu Xu, Hang Zhang, Yu Zhang, Hao Cui, Hao Jia, Xiu-Jie Wang, Jiangping Song","doi":"10.1038/s44161-024-00464-6","DOIUrl":"10.1038/s44161-024-00464-6","url":null,"abstract":"Common arterial grafts used in coronary artery bypass grafting include internal thoracic artery (ITA), radial artery (RA) and right gastroepiploic artery (RGA) grafts; of these, the ITA has the best clinical outcome. Here, by analyzing the single-cell transcriptome of different arterial grafts, we suggest optimization strategies for the RA and RGA based on the ITA as a reference. Compared with the ITA, the RA had more lipid-handling-related CD36+ endothelial cells. Vascular smooth muscle cells from the RGA were more susceptible to spasm, followed by those from the RA; comparison with the ITA suggested that potassium channel openers may counteract vasospasm. Fibroblasts from the RA and RGA highly expressed GDF10 and CREB5, respectively; both GDF10 and CREB5 are associated with extracellular matrix deposition. Cell–cell communication analysis revealed high levels of macrophage migration inhibitory factor signaling in the RA. Administration of macrophage migration inhibitory factor inhibitor to mice with partial carotid artery ligation blocked neointimal hyperplasia induced by disturbed flow. Modulation of identified targets may have protective effects on arterial grafts. Based on comparative single-cell transcriptomics of arterial grafts deriving from internal thoracic, radial and right gastroepiploic arteries, Hu, Dai, Chang, et al. identify factors that might prevent extracellular matrix deposition and fibrosis and improve the outcomes of coronary artery bypass grafting.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"541-557"},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656620","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}

{"title":"Neutrophil extracellular traps trigger IgA loss after stroke and myocardial infarction","authors":"","doi":"10.1038/s44161-024-00465-5","DOIUrl":"10.1038/s44161-024-00465-5","url":null,"abstract":"The mechanisms by which stroke and myocardial infarction trigger lymphocyte loss remain poorly defined. This study shows that the release of neutrophil extracellular traps (NETs) after stroke and myocardial infarction triggers B cell apoptosis and reduces the number of IgA-producing plasma cells. Therapeutic targeting of NETs is immunoprotective in mice and humans.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"496-497"},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140659732","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}