Circulating extracellular RNAs, myocardial remodeling, and heart failure in patients with acute coronary syndrome
AuthorsTran, Khanh-Van T.
Aurigemma, Gerard P.
Lessard, Darleen M.
Shaikh, Amir Y.
Tanriverdi, Selim E.
Keaney, John F. Jr.
Kiefe, Catarina I.
McManus, David D.
Freedman, Jane E.
UMass Chan AffiliationsGraduate School of Biomedical Sciences
Department of Population and Quantitative Health Sciences
Department of Medicine, Division of Cardiovascular Medicine
Document TypeJournal Article
Analytical, Diagnostic and Therapeutic Techniques and Equipment
Nucleic Acids, Nucleotides, and Nucleosides
Translational Medical Research
MetadataShow full item record
AbstractBackground: 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-beta signaling 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.
J Clin Transl Res. 2019 Jun 8;5(1):33-43. eCollection 2019 Sep 8.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/41198
RightsCopyright © 2019, Whioce Publishing Pte. Ltd. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This work is licensed under a Creative Commons Attribution 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as Copyright © 2019, Whioce Publishing Pte. Ltd. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This work is licensed under a Creative Commons Attribution 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/