JACC: Basic to Translational Science最新文献

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"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":null,"pages":null},"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}

{"title":"A Murine Model of mRNA COVID-19 Vaccine-Induced Myocarditis","authors":"","doi":"10.1016/j.jacbts.2024.05.005","DOIUrl":"10.1016/j.jacbts.2024.05.005","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002122/pdfft?md5=5433403652488f87bc773f7fd976233c&pid=1-s2.0-S2452302X24002122-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077106","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}

{"title":"Full Issue PDF","authors":"","doi":"10.1016/S2452-302X(24)00284-5","DOIUrl":"10.1016/S2452-302X(24)00284-5","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002845/pdfft?md5=59aadfba7d1ab7283f68a00310dac332&pid=1-s2.0-S2452302X24002845-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142076974","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}

{"title":"Novel Mechanisms of Postural Hyperventilation in Postural Orthostatic Tachycardia Syndrome","authors":"","doi":"10.1016/j.jacbts.2024.05.010","DOIUrl":"10.1016/j.jacbts.2024.05.010","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002171/pdfft?md5=eb0a556a7ccd0b78a7f59c29c262b9e7&pid=1-s2.0-S2452302X24002171-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142075975","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}

{"title":"Beta Testing New Roles of Cyclic Guanosine Monophosphate in Cardiac Myocyte Contractility","authors":"","doi":"10.1016/j.jacbts.2024.05.012","DOIUrl":"10.1016/j.jacbts.2024.05.012","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002195/pdfft?md5=729fa7fb683bc212369c1b3f324b148d&pid=1-s2.0-S2452302X24002195-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142076943","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}

{"title":"Reassessing the Mechanisms of PLN-R14del Cardiomyopathy","authors":"","doi":"10.1016/j.jacbts.2024.02.017","DOIUrl":"10.1016/j.jacbts.2024.02.017","url":null,"abstract":"<div><p>The phospholamban (PLN) pathogenic gene variant, p.Arg14del (PLN-R14del), can lead to dilated and arrhythmogenic cardiomyopathy, resulting in heart failure. PLN-R14del cardiomyopathy has been conceptualized as a disease caused by sarco/endoplasmic reticulum calcium adenosine triphosphatase 2a (SERCA2a) superinhibition. However, recent studies raised controversy regarding the effect of PLN-R14del on SERCA activity and revealed a prominent role for abnormal PLN protein distribution and sarco/endoplasmic reticulum disorganization as underlying disease mechanism. Strategies targeting sarco/endoplasmic reticulum malformation may, therefore, prove more effective than SERCA activity modulation. This review reassesses the disease mechanisms of PLN-R14del cardiomyopathy and emphasizes the importance of dissecting the underlying molecular mechanisms to uncover targets for innovative treatments.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24000962/pdfft?md5=bcabe0e2e6fb2ba5c06431d948285875&pid=1-s2.0-S2452302X24000962-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140793502","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}

{"title":"How Clonal Hematopoiesis Can Predict Treatment Response in Patients With Dilated Cardiomyopathy","authors":"","doi":"10.1016/j.jacbts.2024.06.002","DOIUrl":"10.1016/j.jacbts.2024.06.002","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002249/pdfft?md5=5b4041d7e33add70878f2a43a3fc9cea&pid=1-s2.0-S2452302X24002249-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142077104","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}

{"title":"Carvedilol Activates a Myofilament Signaling Circuitry to Restore Cardiac Contractility in Heart Failure","authors":"","doi":"10.1016/j.jacbts.2024.03.007","DOIUrl":"10.1016/j.jacbts.2024.03.007","url":null,"abstract":"<div><p>Phosphorylation of myofilament proteins critically regulates beat-to-beat cardiac contraction and is typically altered in heart failure (HF). β-Adrenergic activation induces phosphorylation in numerous substrates at the myofilament. Nevertheless, how cardiac β-adrenoceptors (βARs) signal to the myofilament in healthy and diseased hearts remains poorly understood. The aim of this study was to uncover the spatiotemporal regulation of local βAR signaling at the myofilament and thus identify a potential therapeutic target for HF. Phosphoproteomic analysis of substrate phosphorylation induced by different βAR ligands in mouse hearts was performed. Genetically encoded biosensors were used to characterize cyclic adenosine and guanosine monophosphate signaling and the impacts on excitation-contraction coupling induced by β₁AR ligands at both the cardiomyocyte and whole-heart levels. Myofilament signaling circuitry was identified, including protein kinase G1 (PKG1)–dependent phosphorylation of myosin light chain kinase, myosin phosphatase target subunit 1, and myosin light chain at the myofilaments. The increased phosphorylation of myosin light chain enhances cardiac contractility, with a minimal increase in calcium (Ca²⁺) cycling. This myofilament signaling paradigm is promoted by carvedilol-induced β₁AR–nitric oxide synthetase 3 (NOS3)–dependent cyclic guanosine monophosphate signaling, drawing a parallel to the β₁AR–cyclic adenosine monophosphate–protein kinase A pathway. In patients with HF and a mouse HF model of myocardial infarction, increasing expression and association of NOS3 with β₁AR were observed. Stimulating β₁AR-NOS3-PKG1 signaling increased cardiac contraction in the mouse HF model. This research has characterized myofilament β₁AR-PKG1-dependent signaling circuitry to increase phosphorylation of myosin light chain and enhance cardiac contractility, with a minimal increase in Ca²⁺ cycling. The present findings raise the possibility of targeting this myofilament signaling circuitry for treatment of patients with HF.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24001049/pdfft?md5=b769b8c6532a03aacea9aeb17875e508&pid=1-s2.0-S2452302X24001049-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142076942","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}