Circulating extracellular RNAs,myocardial remodeling,and heart failure in patients with acute coronary syndrome  

作　　者：Khanh-Van Tran Kahraman Tanriverdi Gerard P.Aurigemma Darleen Lessard Mayank Sardana Matthew Parker Amir Shaikh Matthew Gottbrecht Zachary Milstone Selim Tanriverdi Olga Vitseva John F.Keaney Catarina I.Kiefe David D.McManus Jane E.Freedman 

机构地区：[1]Department of Medicine,University of Massachusetts Medical School,Worcester,MA,USA [2]Population and Quantitative Health Sciences University of Massachusetts Medical School,Worcester,MA,USA

出　　处：《Journal of Clinical & Translational Research》2019年第1期33-43,共11页临床和转化研究

基　　金：This work was supported by 5T32HL120823(KVT),1U01HL105268,R01HL126911(DDM),R01HL137734(DDM),R01HL137794(DDM),R01HL13660(DDM);R01HL141434(DDM)from the National Heart,Lung and Blood Institute;Grant1522052 from the National Science Foundation(DDM);16SFRN31740000 from the American Heart Association(JEF);RFA-HL-12-008(JEF),RO1 HL087201A(JEF,KT),RFAHL-12-008(JEF);U01HL105268(CIK from the National Heart,Lung and Blood Institute of the National Institutes of Health.

摘　　要：Background:Given high on-treatment mortality in heart failure(HF),identifying molecular pathways that underlie adverse cardiac remodeling may offer novel biomarkers and therapeutic avenues.Circulating extracellular RNAs(ex-RNAs)regulate important biological processes and are emerging as biomarkers of disease,but less is known about their role in the acute setting,particularly in the setting of HF.Methods:We examined the ex-RNA profiles of 296 acute coronary syndrome(ACS)survivors enrolled in the Transitions,Risks,and Actions in Coronary Events Center for Outcomes Research and Education Cohort.We measured 374 ex-RNAs selected a priori,based on previous findings from a large population study.We employed a two-step,mechanism-driven approach to identify ex-RNAs associated with echocardiographic phenotypes(left ventricular[LV]ejection fraction,LV mass,LV end-diastolic volume,left atrial[LA]dimension,and LA volume index)then tested relations of these ex-RNAs with prevalent HF(N=31,10.5%).We performed further bioinformatics analysis of microRNA(miRNAs)predicted targets’genes ontology categories and molecular pathways.Results:We identified 44 ex-RNAs associated with at least one echocardiographic phenotype associated with HF.Of these 44 exRNAs,miR-29-3p,miR-584-5p,and miR-1247-5p were also associated with prevalent HF.The three microRNAs were implicated in the regulation p53 and transforming growth factor-βsignaling pathways and predicted to be involved in cardiac fibrosis and cell death;miRNA predicted targets were enriched in gene ontology categories including several involving the extracellular matrix and cellular differentiation.Conclusions:Among ACS survivors,we observed that miR-29-3p,miR-584-5p,and miR-1247-5p were associated with both echocardiographic markers of cardiac remodeling and prevalent HF.Relevance for Patients:miR-29c-3p,miR-584-5p,and miR-1247-5p were associated with echocardiographic phenotypes and prevalent HF and are potential biomarkers for adverse cardiac remodeling in HF.

关 键 词：EXTRACELLULAR RNAS Heart failure Cardiac REMODELING Echocardiographic PHENOTYPES Biomarkers 

分 类 号：R54[医药卫生—心血管疾病]