Pub Date : 2024-10-01DOI: 10.1016/j.jacbts.2024.08.007
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}
Pub Date : 2024-10-01DOI: 10.1016/j.jacbts.2024.07.011
Gary F. Mitchell MD
{"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}
Pub Date : 2024-10-01DOI: 10.1016/j.jacbts.2024.05.017
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
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.
导致大动脉僵化（LAS）的分子机制尚不完全清楚。本研究旨在通过蛋白质组和基因组互补分析，研究循环血浆蛋白与大动脉僵化之间的关联。在 Asklepios 研究队列中的 1178 人中，共鉴定出 106 种与颈动脉-股动脉脉搏波速度（LAS 的无创测量指标）相关的蛋白质。孟德尔随机分析显示，13 种基因预测的血浆蛋白对脉压有因果效应，包括软骨中间层蛋白-2、高温要求 A 丝氨酸肽酶-1 和神经元生长因子-1。这些发现为减少 LAS 及其相关疾病提供了潜在的新治疗靶点。
{"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}
Pub Date : 2024-10-01DOI: 10.1016/j.jacbts.2024.05.011
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
Dilated cardiomyopathy (DCM) is associated with high mortality despite advanced therapies. The LMNA 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 Lmna–/– 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 Lmna–/– hearts. Moreover, early injured mitochondria with decreased cristae density and sirtuin 1 (SIRT1) down-regulation were observed in 2-week-old Lmna–/– 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 Lmna–/– mice. Mechanistically, LMNA 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 LMNA mutation–associated DCM.
{"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}
Pub Date : 2024-10-01DOI: 10.1016/j.jacbts.2024.07.007
Chia-Feng Liu PhD , W.H. Wilson Tang MD
{"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}
Pub Date : 2024-10-01DOI: 10.1016/j.jacbts.2024.09.005
Martin Young DPhil, Douglas L. Mann MD (Editor-in-Chief, JACC: Basic to Translational Science)
{"title":"Addressing the Reproducibility Crisis in Science","authors":"Martin Young DPhil, Douglas L. Mann MD (Editor-in-Chief, JACC: Basic to Translational Science)","doi":"10.1016/j.jacbts.2024.09.005","DOIUrl":"10.1016/j.jacbts.2024.09.005","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 10","pages":"Pages 1266-1267"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142530100","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 more prevalent in men than in women, with endothelial dysfunction, prodromal to CAD, developing a decade earlier in middle-aged men. We investigated the molecular basis of this dimorphism ex vivo in arterial segments discarded during surgery of CAD patients. The results reveal a lower endothelial relaxant sensitivity in men, and a senescence-associated inflammaging transcriptomic signature in endothelial cells. In women, cellular metabolism and endothelial maintenance pathways are conserved. This suggests that senolytic therapies to reduce risk of cardiovascular events in women with CAD may not be as effective as in men.
{"title":"Senescence and Inflamm-Aging Are Associated With Endothelial Dysfunction in Men But Not Women With Atherosclerosis","authors":"Pauline Mury PhD , Gael Cagnone PhD , Olina Dagher MD , Florian Wünnemann PhD , Guillaume Voghel MD, PhD , Melissa Beaudoin MSc , Mélanie Lambert PhD , Géraldine Miquel BSc , Pierre-Emmanuel Noly MD, PhD , Louis P. Perrault MD, PhD , Michel Carrier MD , Nathalie Thorin-Trescases PhD , Jean-Sébastien Joyal MD, PhD , Guillaume Lettre PhD , Eric Thorin PhD","doi":"10.1016/j.jacbts.2024.06.012","DOIUrl":"10.1016/j.jacbts.2024.06.012","url":null,"abstract":"<div><div>Coronary artery disease (CAD) is more prevalent in men than in women, with endothelial dysfunction, prodromal to CAD, developing a decade earlier in middle-aged men. We investigated the molecular basis of this dimorphism ex vivo in arterial segments discarded during surgery of CAD patients. The results reveal a lower endothelial relaxant sensitivity in men, and a senescence-associated inflammaging transcriptomic signature in endothelial cells. In women, cellular metabolism and endothelial maintenance pathways are conserved. This suggests that senolytic therapies to reduce risk of cardiovascular events in women with CAD may not be as effective as in men.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 10","pages":"Pages 1163-1177"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142530872","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 : 2024-10-01DOI: 10.1016/j.jacbts.2024.05.015
Vitali Rusinkevich MD, MS, PhD , David Elias BS , Monica Vladut Talor MSc , Daniela Čiháková MD, PhD
Intrapericardial delivery offers a route for heart therapies. Mouse heart size and membrane thickness pose catheterization challenges, hampering pericardium-targeted treatments. The objectives were to develop a mouse surgical technique for pericardial catheter insertion and to assess its suitability for intrapericardial delivery, including use with a myocardial ischemia/reperfusion model. We used successful catheter implantation in BALB/cJ and ΔdblGATA1 mice, showcasing intrapericardial delivery with fluorescent beads and eosinophils. We demonstrated a combination of pericardial catheterization with myocardial ischemia/reperfusion model. A reliable catheterization technique, enabling intrapericardial delivery of therapeutic agents in mice provides a valuable tool for studying the pericardial space and mediastinum in basic and translational research.
{"title":"The Technique of Permanent Pericardial Catheter in Mice","authors":"Vitali Rusinkevich MD, MS, PhD , David Elias BS , Monica Vladut Talor MSc , Daniela Čiháková MD, PhD","doi":"10.1016/j.jacbts.2024.05.015","DOIUrl":"10.1016/j.jacbts.2024.05.015","url":null,"abstract":"<div><div>Intrapericardial delivery offers a route for heart therapies. Mouse heart size and membrane thickness pose catheterization challenges, hampering pericardium-targeted treatments. The objectives were to develop a mouse surgical technique for pericardial catheter insertion and to assess its suitability for intrapericardial delivery, including use with a myocardial ischemia/reperfusion model. We used successful catheter implantation in BALB/cJ and ΔdblGATA1 mice, showcasing intrapericardial delivery with fluorescent beads and eosinophils. We demonstrated a combination of pericardial catheterization with myocardial ischemia/reperfusion model. A reliable catheterization technique, enabling intrapericardial delivery of therapeutic agents in mice provides a valuable tool for studying the pericardial space and mediastinum in basic and translational research.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 10","pages":"Pages 1234-1247"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142530096","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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