{"title":"Targeting USP25 in the Heart","authors":"Hanming Zhang PhD","doi":"10.1016/j.jacbts.2024.08.001","DOIUrl":"10.1016/j.jacbts.2024.08.001","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 11","pages":"Pages 1305-1307"},"PeriodicalIF":8.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697691","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}
Mona E. Ahmed MD, PhD , David M. Leistner MD , Diaa Hakim MD, PhD , Youssef Abdelwahed MD , Ahmet U. Coskun PhD , Charles Maynard PhD , Claudio Seppelt MD , Gregor Nelles MD , Denitsa Meteva MD , Nicholas V. Cefalo BS , Peter Libby MD , Ulf Landmesser MD , Peter H. Stone MD
{"title":"Endothelial Shear Stress Metrics Associate With Proinflammatory Pathways at the Culprit Site of Coronary Erosion","authors":"Mona E. Ahmed MD, PhD , David M. Leistner MD , Diaa Hakim MD, PhD , Youssef Abdelwahed MD , Ahmet U. Coskun PhD , Charles Maynard PhD , Claudio Seppelt MD , Gregor Nelles MD , Denitsa Meteva MD , Nicholas V. Cefalo BS , Peter Libby MD , Ulf Landmesser MD , Peter H. Stone MD","doi":"10.1016/j.jacbts.2024.07.008","DOIUrl":"10.1016/j.jacbts.2024.07.008","url":null,"abstract":"<div><div>Low endothelial shear stress (ESS) and associated adverse biomechanical features stimulate inflammation, contribute to atherogenesis, and predispose to coronary plaque disruption. The mechanistic links between adverse flow-related hemodynamics and inflammatory mediators implicated in plaque erosion, however, remain little explored. We investigated the relationship of high-risk ESS metrics to culprit lesion proinflammatory/proatherogenic cells and cytokines/chemokines implicated in coronary plaque erosion in patients with acute coronary syndromes. In eroded plaques, low ESS, high ESS gradient, and steepness of plaque topographical slope associated with increased numbers of local T cells and subsets (CD4<sup>+</sup>, CD8<sup>+</sup>, natural killer T cells) as well as inflammatory mediators (interleukin [IL]-6, macrophage inflammatory protein-1β, IL-1β, IL-2).</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 11","pages":"Pages 1269-1283"},"PeriodicalIF":8.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698425","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}
Marijn C. Peters PhD , Arnaud Zaldumbide PhD , Esmee J. Groeneveld BSc , Martijn J.W.E. Rabelink BSc , Janneke H. Peerlings MSc , Antoon van den Bogaerdt MSc , Carlijn V.C. Bouten PhD , Rob C. Hoeben PhD , Marie-Jose Goumans PhD , Abraham van Wijk MD, PhD
{"title":"Immune Shielding of Human Heart Valves","authors":"Marijn C. Peters PhD , Arnaud Zaldumbide PhD , Esmee J. Groeneveld BSc , Martijn J.W.E. Rabelink BSc , Janneke H. Peerlings MSc , Antoon van den Bogaerdt MSc , Carlijn V.C. Bouten PhD , Rob C. Hoeben PhD , Marie-Jose Goumans PhD , Abraham van Wijk MD, PhD","doi":"10.1016/j.jacbts.2024.07.003","DOIUrl":"10.1016/j.jacbts.2024.07.003","url":null,"abstract":"<div><div>Children born with defective heart valves require multiple donor valve replacements throughout life, because these cannot grow and can cause early failure through immune degeneration. This study tests the lentiviral delivery of viral immune evasion genes US2 and human serpin 9 to shield human heart valves from immune rejection. The results show we can efficiently down-regulate human leukocyte antigen expression in heart valve cells and in intact heart valve tissue resulting in decreased activity of a human leukocyte antigen–reactive CD8+ T-cell clone without inducing cytotoxicity. This study demonstrates immune shielding of human heart valves and brings us closer to a durable valve graft in pediatric patients.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 11","pages":"Pages 1345-1359"},"PeriodicalIF":8.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697695","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}
Douglas L. Mann MD (Editor-in-Chief: JACC: Basic to Translational Science)
{"title":"Recognizing Early Career Translational Investigators","authors":"Douglas L. Mann MD (Editor-in-Chief: JACC: Basic to Translational Science)","doi":"10.1016/j.jacbts.2024.10.001","DOIUrl":"10.1016/j.jacbts.2024.10.001","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 11","pages":"Page 1375"},"PeriodicalIF":8.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697831","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}
Pedro Mendes-Ferreira PhD , André M. Leite-Moreira MD, MS , Adelino F. Leite-Moreira MD, PhD
{"title":"Reverse Translation of Pericardial Access","authors":"Pedro Mendes-Ferreira PhD , André M. Leite-Moreira MD, MS , Adelino F. Leite-Moreira MD, PhD","doi":"10.1016/j.jacbts.2024.08.007","DOIUrl":"10.1016/j.jacbts.2024.08.007","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 10","pages":"Pages 1248-1249"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142530097","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":"Proteomics of Large Artery Stiffness","authors":"Gary F. Mitchell MD","doi":"10.1016/j.jacbts.2024.07.011","DOIUrl":"10.1016/j.jacbts.2024.07.011","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 10","pages":"Pages 1192-1194"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142530877","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}
Marie-Joe Dib PhD , Joe David Azzo MD , Lei Zhao MD, PhD , Oday Salman MD , Sushrima Gan PhD , Marc L. De Buyzere MSc , Tim De Meyer PhD , Christina Ebert PhD , Kushan Gunawardhana PhD , Laura Liu PhD , David Gordon PhD , Dietmar Seiffert MD, PhD , Chang Ching-Pin MD, PhD , Payman Zamani MD, MTR , Jordana B. Cohen MD, MSCE , Bianca Pourmussa BA , Seavmeiyin Kun BA , Dipender Gill MD, PhD , Stephen Burgess PhD , Vanessa van Empel MD , Julio A. Chirinos MD, PhD
{"title":"Proteome-Wide Genetic Investigation of Large Artery Stiffness","authors":"Marie-Joe Dib PhD , Joe David Azzo MD , Lei Zhao MD, PhD , Oday Salman MD , Sushrima Gan PhD , Marc L. De Buyzere MSc , Tim De Meyer PhD , Christina Ebert PhD , Kushan Gunawardhana PhD , Laura Liu PhD , David Gordon PhD , Dietmar Seiffert MD, PhD , Chang Ching-Pin MD, PhD , Payman Zamani MD, MTR , Jordana B. Cohen MD, MSCE , Bianca Pourmussa BA , Seavmeiyin Kun BA , Dipender Gill MD, PhD , Stephen Burgess PhD , Vanessa van Empel MD , Julio A. Chirinos MD, PhD","doi":"10.1016/j.jacbts.2024.05.017","DOIUrl":"10.1016/j.jacbts.2024.05.017","url":null,"abstract":"<div><div>The molecular mechanisms contributing to large artery stiffness (LAS) are not fully understood. The aim of this study was to investigate the association between circulating plasma proteins and LAS using complementary proteomic and genomic analyses. A total of 106 proteins associated with carotid-femoral pulse-wave velocity, a noninvasive measure of LAS, were identified in 1,178 individuals from the Asklepios study cohort. Mendelian randomization analyses revealed causal effects of 13 genetically predicted plasma proteins on pulse pressure, including cartilage intermediate layer protein-2, high-temperature requirement A serine peptidase-1, and neuronal growth factor-1. These findings suggest potential novel therapeutic targets to reduce LAS and its related diseases.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 10","pages":"Pages 1178-1191"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142530873","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}
Zunhui Du MS , Yanting Zhou MS , Qiheng Li MS , Yuan Xie MS , Tingfang Zhu MS , Jing Qiao MS , Ruihong Zhang BS , Yangyang Bao MD, PhD , Lingjie Wang MD, PhD , Yinyin Xie PhD , Jinwei Quan MS , Menglu Lin MS , Ning Zhang MD, PhD , Qi Jin MD, PhD , Wenbin Liang MD, PhD , Liqun Wu MD, PhD , Tong Yin MD, PhD , Yucai Xie MD, PhD
{"title":"SIRT1 Ameliorates Lamin A/C Deficiency-Induced Cardiac Dysfunction by Promoting Mitochondrial Bioenergetics","authors":"Zunhui Du MS , Yanting Zhou MS , Qiheng Li MS , Yuan Xie MS , Tingfang Zhu MS , Jing Qiao MS , Ruihong Zhang BS , Yangyang Bao MD, PhD , Lingjie Wang MD, PhD , Yinyin Xie PhD , Jinwei Quan MS , Menglu Lin MS , Ning Zhang MD, PhD , Qi Jin MD, PhD , Wenbin Liang MD, PhD , Liqun Wu MD, PhD , Tong Yin MD, PhD , Yucai Xie MD, PhD","doi":"10.1016/j.jacbts.2024.05.011","DOIUrl":"10.1016/j.jacbts.2024.05.011","url":null,"abstract":"<div><div>Dilated cardiomyopathy (DCM) is associated with high mortality despite advanced therapies. The <em>LMNA</em> gene encodes lamin A/C and is the second most frequently mutated gene associated with DCM, for which therapeutic options are limited. Here we generated <em>Lmna</em><sup>–/–</sup> mice and found they exhibited cardiac dysfunction at the age of 1 month but not at 2 weeks. Proteomics showed down-regulation of mitochondrial function–related pathways in <em>Lmna</em><sup>–/–</sup> hearts. Moreover, early injured mitochondria with decreased cristae density and sirtuin 1 (SIRT1) down-regulation were observed in 2-week-old <em>Lmna</em><sup>–/–</sup> hearts. Adenoviral overexpression of SIRT1 in lamin A/C knockdown neonatal rat ventricular myocytes improved mitochondrial oxidative respiration capacity. Adeno-associated virus–mediated SIRT1 overexpression alleviated mitochondrial injury, cardiac systolic dysfunction, ventricular dilation, and fibrosis, and prolonged lifespan in <em>Lmna</em><sup>–/–</sup> mice. Mechanistically, <em>LMNA</em> maintains mitochondrial bioenergetics through the SIRT1-PARKIN axis. Our results suggest that targeting the SIRT1 signaling pathway is expected to be a novel therapeutic strategy for <em>LMNA</em> mutation–associated DCM.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 10","pages":"Pages 1211-1230"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142530094","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":"Targeting Mitochondria Dysfunction in LMNA Cardiomyopathy","authors":"Chia-Feng Liu PhD , W.H. Wilson Tang MD","doi":"10.1016/j.jacbts.2024.07.007","DOIUrl":"10.1016/j.jacbts.2024.07.007","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 10","pages":"Pages 1231-1233"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142530095","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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