Pub Date : 2024-09-01DOI: 10.1016/j.jacbts.2024.05.016
Pedro Giro MD , Mallory Filipp PhD , Michael J. Zhang MD, PhD , Ethan D. Moser MPH , Edward B. Thorp PhD , Prarthana J. Dalal MD, PhD , Ravi V. Shah MD , Patrick T. Ellinor MD, PhD , Jonathan W. Cunningham MD , Sean J. Jurgens MD, MSc , Arjun Sinha MD, MSc , Laura Rasmussen-Torvik PhD, MPH , Jorge Kizer MD, MSc , Kent D. Taylor PhD , Philip Greenland MD , Bruce M. Psaty MD, PhD , Russell P. Tracy PhD , Lin Yee Chen MD, MS , Amil M. Shah MD , Bing Yu PhD , Ravi B. Patel MD, MSc
A common missense variant in ICAM1 among African American individuals (rs5491; pK56M) has been associated with risk of heart failure with preserved ejection fraction (HFpEF), but the pathways that lead to HFpEF among those with this variant are not clear. In this analysis of 92 circulating proteins and their associated networks, we identified 7 circulating inflammatory proteins associated with rs5491 among >600 African American individuals. Using weighted coexpression network analysis, 3 protein networks were identified, one of which was associated with rs5491. This protein network was most highly represented by members of the tumor necrosis receptor superfamily. The rs5491 variant demonstrated an inflammatory proteomic profile in a separate cohort of African American individuals. This analysis identifies inflammatory pathways that may drive HFpEF among African American individuals with the ICAM1 pK56M (rs5491) variant.
{"title":"Proteomic Profile of the ICAM1 p.K56M HFpEF Risk Variant","authors":"Pedro Giro MD , Mallory Filipp PhD , Michael J. Zhang MD, PhD , Ethan D. Moser MPH , Edward B. Thorp PhD , Prarthana J. Dalal MD, PhD , Ravi V. Shah MD , Patrick T. Ellinor MD, PhD , Jonathan W. Cunningham MD , Sean J. Jurgens MD, MSc , Arjun Sinha MD, MSc , Laura Rasmussen-Torvik PhD, MPH , Jorge Kizer MD, MSc , Kent D. Taylor PhD , Philip Greenland MD , Bruce M. Psaty MD, PhD , Russell P. Tracy PhD , Lin Yee Chen MD, MS , Amil M. Shah MD , Bing Yu PhD , Ravi B. Patel MD, MSc","doi":"10.1016/j.jacbts.2024.05.016","DOIUrl":"10.1016/j.jacbts.2024.05.016","url":null,"abstract":"<div><div>A common missense variant in <em>ICAM1</em> among African American individuals (rs5491; pK56M) has been associated with risk of heart failure with preserved ejection fraction (HFpEF), but the pathways that lead to HFpEF among those with this variant are not clear. In this analysis of 92 circulating proteins and their associated networks, we identified 7 circulating inflammatory proteins associated with rs5491 among >600 African American individuals. Using weighted coexpression network analysis, 3 protein networks were identified, one of which was associated with rs5491. This protein network was most highly represented by members of the tumor necrosis receptor superfamily. The rs5491 variant demonstrated an inflammatory proteomic profile in a separate cohort of African American individuals. This analysis identifies inflammatory pathways that may drive HFpEF among African American individuals with the <em>ICAM1</em> pK56M (rs5491) variant.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 9","pages":"Pages 1073-1084"},"PeriodicalIF":8.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002262/pdfft?md5=6a8e1da15f7d8bf280efb89154fd82d8&pid=1-s2.0-S2452302X24002262-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Coronary artery disease (CAD) is a major health issue. This study focused on pericardial macrophages and small extracellular vesicles (sEVs) in CAD. The macrophages in CAD patients showed reduced expression of protective markers and unchanged levels of proinflammatory receptors. Similar changes were observed in buffy-coat–derived macrophages when stimulated with CAD pericardial fluid-derived sEVs. The sEV contained miRNA-6516-5p, which inhibited CD36 and affected macrophage lipid uptake. These findings indicate that sEV-mediated miRNA actions contribute to the decrease in protective pericardial macrophages in CAD.
{"title":"Small Extracellular Vesicles in the Pericardium Modulate Macrophage Immunophenotype in Coronary Artery Disease","authors":"Soumaya Ben-Aicha PhD , Maryam Anwar PhD , Gemma Vilahur PhD , Fabiana Martino PhD , Panagiotis G. Kyriazis MSc , Natasha de Winter MSc , Prakash P. Punjabi MD, PhD , Gianni D. Angelini MD , Susanne Sattler PhD , Costanza Emanueli PhD","doi":"10.1016/j.jacbts.2024.05.003","DOIUrl":"10.1016/j.jacbts.2024.05.003","url":null,"abstract":"<div><div>Coronary artery disease (CAD) is a major health issue. This study focused on pericardial macrophages and small extracellular vesicles (sEVs) in CAD. The macrophages in CAD patients showed reduced expression of protective markers and unchanged levels of proinflammatory receptors. Similar changes were observed in buffy-coat–derived macrophages when stimulated with CAD pericardial fluid-derived sEVs. The sEV contained miRNA-6516-5p, which inhibited CD36 and affected macrophage lipid uptake. These findings indicate that sEV-mediated miRNA actions contribute to the decrease in protective pericardial macrophages in CAD.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 9","pages":"Pages 1057-1072"},"PeriodicalIF":8.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24001888/pdfft?md5=a5069912a4a92134ebda4433d621f0d5&pid=1-s2.0-S2452302X24001888-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141703465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/j.jacbts.2024.08.002
Douglas L. Mann MD (Editor-in-Chief, JACC: Basic to Translational Science)
{"title":"The Use of Digital Healthcare Twins in Early-Phase Clinical Trials","authors":"Douglas L. Mann MD (Editor-in-Chief, JACC: Basic to Translational Science)","doi":"10.1016/j.jacbts.2024.08.002","DOIUrl":"10.1016/j.jacbts.2024.08.002","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 9","pages":"Pages 1159-1161"},"PeriodicalIF":8.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002936/pdfft?md5=cb67a842585465ea6128136fadae1e91&pid=1-s2.0-S2452302X24002936-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/j.jacbts.2024.07.004
Thomas M. Vondriska PhD , David J. Lefer PhD
{"title":"“Circulating Inflammation” and the Plasma Proteome in Heart Failure With Preserved Ejection Fraction","authors":"Thomas M. Vondriska PhD , David J. Lefer PhD","doi":"10.1016/j.jacbts.2024.07.004","DOIUrl":"10.1016/j.jacbts.2024.07.004","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 9","pages":"Pages 1085-1087"},"PeriodicalIF":8.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002614/pdfft?md5=3cfd1d18ff0b9c640a8524bcd25ab645&pid=1-s2.0-S2452302X24002614-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/j.jacbts.2024.06.009
Marco Andreis MD , Nazareno Paolocci MD, PhD
{"title":"TRIM55: An Enemy at the Post-MI Border?","authors":"Marco Andreis MD , Nazareno Paolocci MD, PhD","doi":"10.1016/j.jacbts.2024.06.009","DOIUrl":"10.1016/j.jacbts.2024.06.009","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 9","pages":"Pages 1123-1125"},"PeriodicalIF":8.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002547/pdfft?md5=de6282ef3290f001d32447e932b42c89&pid=1-s2.0-S2452302X24002547-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.1016/j.jacbts.2024.04.008
Virginia S. Hahn MD , Senthil Selvaraj MD, MS, MA , Kavita Sharma MD , Svati H. Shah MD, MHS
Both heart failure and cardiometabolic disease are on the rise, and abnormal cardiac and peripheral metabolism are central to the syndrome of heart failure. Advances in metabolomic profiling have improved our understanding of the heart’s metabolic flexibility in patients with and without heart failure. Prior studies have noted patients with heart failure display metabolomic profiles associated with marked abnormalities in the metabolism of fatty acids, branched-chain amino acids, ketones, and glucose compared with control subjects. Metabolomics can highlight specific pathways that are dysregulated; however, other metabolites beyond those related to fuel metabolism may also play a role in precision-medicine approaches. Novel approaches include metabolic flux studies, spatial and single-cell analysis, serial monitoring of treatment response, and integration with other -omics data. The goal of these innovative approaches should be to harness metabolomic technologies to affect precision care for patients with heart failure.
{"title":"Towards Metabolomic-Based Precision Approaches for Classifying and Treating Heart Failure","authors":"Virginia S. Hahn MD , Senthil Selvaraj MD, MS, MA , Kavita Sharma MD , Svati H. Shah MD, MHS","doi":"10.1016/j.jacbts.2024.04.008","DOIUrl":"10.1016/j.jacbts.2024.04.008","url":null,"abstract":"<div><div>Both heart failure and cardiometabolic disease are on the rise, and abnormal cardiac and peripheral metabolism are central to the syndrome of heart failure. Advances in metabolomic profiling have improved our understanding of the heart’s metabolic flexibility in patients with and without heart failure. Prior studies have noted patients with heart failure display metabolomic profiles associated with marked abnormalities in the metabolism of fatty acids, branched-chain amino acids, ketones, and glucose compared with control subjects. Metabolomics can highlight specific pathways that are dysregulated; however, other metabolites beyond those related to fuel metabolism may also play a role in precision-medicine approaches. Novel approaches include metabolic flux studies, spatial and single-cell analysis, serial monitoring of treatment response, and integration with other -omics data. The goal of these innovative approaches should be to harness metabolomic technologies to affect precision care for patients with heart failure.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 9","pages":"Pages 1144-1158"},"PeriodicalIF":8.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24001773/pdfft?md5=38912ce373f5c15c65c5656b08679e0b&pid=1-s2.0-S2452302X24001773-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.1016/j.jacbts.2024.08.003
Panagiota-Efstathia Nikolaou PhD, Lara S.F. Konijnenberg MD PhD, Ioannis V. Kostopoulos PhD, Marios Miliotis PhD, Nikolaos Mylonas MSc, Anastasios Georgoulis PhD, George Pavlidis MD PhD, Carolien T.A. Kuster Msc, Vince P.A. van Reijmersdal Msc, Tom T.J. Luiken Msc, Anna Agapaki PhD, Rona Roverts PhD, Nikolaos Orologas PhD, Dimitris Grigoriadis PhD, Gaëtan Pallot PhD, Pierre Boucher MSc, Nikolaos Kostomitsopoulos PhD, Michael Paul Pieper PhD, Stéphane Germain PhD, Yannis Loukas PhD, Yannis Dotsikas PhD, Ignatios Ikonomidis MD PhD, Artemis G. Hatzigeorgiou PhD, Ourania Tsitsilonis MD PhD, Coert J. Zuurbier PhD, Robin Nijveldt MD PhD, Niels van Royen MD PhD, Ioanna Andreadou PhD
Empagliflozin treatment before acute myocardial infarction mainly targets the endothelial cell transcriptome. Empagliflozin treatment before and after myocardial infarction decreased no reflow and microvascular injury, leading to reduced infiltration of inflammatory cells, reduced infarct size, and improved cardiac function in mice. In diabetic patients receiving empagliflozin after myocardial infarction, perfused boundary region, flow-mediated dilation, and global longitudinal strain were improved.
{"title":"Empagliflozin in Acute Myocardial Infarction Reduces No-Reflow and Preserves Cardiac Function by Preventing Endothelial Damage","authors":"Panagiota-Efstathia Nikolaou PhD, Lara S.F. Konijnenberg MD PhD, Ioannis V. Kostopoulos PhD, Marios Miliotis PhD, Nikolaos Mylonas MSc, Anastasios Georgoulis PhD, George Pavlidis MD PhD, Carolien T.A. Kuster Msc, Vince P.A. van Reijmersdal Msc, Tom T.J. Luiken Msc, Anna Agapaki PhD, Rona Roverts PhD, Nikolaos Orologas PhD, Dimitris Grigoriadis PhD, Gaëtan Pallot PhD, Pierre Boucher MSc, Nikolaos Kostomitsopoulos PhD, Michael Paul Pieper PhD, Stéphane Germain PhD, Yannis Loukas PhD, Yannis Dotsikas PhD, Ignatios Ikonomidis MD PhD, Artemis G. Hatzigeorgiou PhD, Ourania Tsitsilonis MD PhD, Coert J. Zuurbier PhD, Robin Nijveldt MD PhD, Niels van Royen MD PhD, Ioanna Andreadou PhD","doi":"10.1016/j.jacbts.2024.08.003","DOIUrl":"https://doi.org/10.1016/j.jacbts.2024.08.003","url":null,"abstract":"Empagliflozin treatment before acute myocardial infarction mainly targets the endothelial cell transcriptome. Empagliflozin treatment before and after myocardial infarction decreased no reflow and microvascular injury, leading to reduced infiltration of inflammatory cells, reduced infarct size, and improved cardiac function in mice. In diabetic patients receiving empagliflozin after myocardial infarction, perfused boundary region, flow-mediated dilation, and global longitudinal strain were improved.","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"14 1","pages":""},"PeriodicalIF":9.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142207141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As major noncardiomyocyte components in cardiac tissues, macrophages and fibroblasts play crucial roles in maintaining cardiac homeostasis, orchestrating reparative responses after cardiac injuries, facilitating adaptive cardiac remodeling, and contributing to adverse cardiac remodeling, owing to their inherent heterogeneity and plasticity. Recent advances in research methods have yielded novel insights into the intricate interactions between macrophages and fibroblasts in the cardiac context. This review aims to comprehensively examine the molecular mechanisms governing macrophage-fibroblast interactions in cardiac homeostasis and remodeling, emphasize recent advancements in the field, and offer an evaluation from a translational standpoint.
{"title":"Emerging Role of Macrophage-Fibroblast Interactions in Cardiac Homeostasis and Remodeling","authors":"Xu-Zhe Zhang MD, Qin-Lin Li MB, Ting-Ting Tang MD PhD, Xiang Cheng MD PhD","doi":"10.1016/j.jacbts.2024.06.003","DOIUrl":"https://doi.org/10.1016/j.jacbts.2024.06.003","url":null,"abstract":"As major noncardiomyocyte components in cardiac tissues, macrophages and fibroblasts play crucial roles in maintaining cardiac homeostasis, orchestrating reparative responses after cardiac injuries, facilitating adaptive cardiac remodeling, and contributing to adverse cardiac remodeling, owing to their inherent heterogeneity and plasticity. Recent advances in research methods have yielded novel insights into the intricate interactions between macrophages and fibroblasts in the cardiac context. This review aims to comprehensively examine the molecular mechanisms governing macrophage-fibroblast interactions in cardiac homeostasis and remodeling, emphasize recent advancements in the field, and offer an evaluation from a translational standpoint.","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"17 1","pages":""},"PeriodicalIF":9.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142207142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.jacbts.2023.12.005
Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Therapeutic agents, such as those that lower low-density lipoprotein cholesterol, have been a critical factor in mitigating CVD event risk and demonstrate the important role that drug discovery plays in reducing morbidity and mortality. However, rapidly rising development costs, diminishing returns, and an increasingly challenging regulatory environment have all contributed to a declining number of cardiovascular (CV) therapeutic agents entering the health care marketplace. For pharmaceutical companies, a traditional cardiovascular outcomes trial (CVOT) can be a major financial burden and impediment to CV agent development. They can take as long as a decade to conduct, delaying potential investment return while carrying risk of failure. For patients, lengthy CVOTs delay drug accessibility. Without cost-effective CVOTs, drug innovation may be compromised, with CV patients bearing the consequences. This paper reviews potential approaches for making CV drug development more cost-effective.
{"title":"The Imperative to Enhance Cost-Effectiveness for Cardiovascular Therapeutic Development","authors":"","doi":"10.1016/j.jacbts.2023.12.005","DOIUrl":"10.1016/j.jacbts.2023.12.005","url":null,"abstract":"<div><p>Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Therapeutic agents, such as those that lower low-density lipoprotein cholesterol, have been a critical factor in mitigating CVD event risk and demonstrate the important role that drug discovery plays in reducing morbidity and mortality. However, rapidly rising development costs, diminishing returns, and an increasingly challenging regulatory environment have all contributed to a declining number of cardiovascular (CV) therapeutic agents entering the health care marketplace. For pharmaceutical companies, a traditional cardiovascular outcomes trial (CVOT) can be a major financial burden and impediment to CV agent development. They can take as long as a decade to conduct, delaying potential investment return while carrying risk of failure. For patients, lengthy CVOTs delay drug accessibility. Without cost-effective CVOTs, drug innovation may be compromised, with CV patients bearing the consequences. This paper reviews potential approaches for making CV drug development more cost-effective.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 8","pages":"Pages 1029-1040"},"PeriodicalIF":8.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24000020/pdfft?md5=f9f873ce4a3421c7208a6be748dfe0f2&pid=1-s2.0-S2452302X24000020-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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