Department of Medicine, Division of Cardiovascular Medicine; Department of Population and Quantitative Health Sciences; Graduate School of Biomedical Sciences
Analytical, Diagnostic and Therapeutic Techniques and Equipment | Biological Factors | Cardiology | Cardiovascular Diseases | Cardiovascular System | Nucleic Acids, Nucleotides, and Nucleosides | Translational Medical Research
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-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.
Biomarkers, Cardiac remodelling, Echocardiographic phenotypes, Extracellular RNAs, Heart failure
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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/
DOI of Published Version
J Clin Transl Res. 2019 Jun 8;5(1):33-43. eCollection 2019 Sep 8.
Journal of clinical and translational research
Tran KT, Tanriverdi K, Aurigemma GP, Lessard DM, Sardana M, Parker M, Shaikh AY, Gottbrecht M, Milstone Z, Tanriverdi SE, Vitseva O, Keaney JF, Kiefe CI, McManus DD, Freedman JE. (2019). Circulating extracellular RNAs, myocardial remodeling, and heart failure in patients with acute coronary syndrome. Open Access Articles. https://doi.org/10.18053/jctres.05.201901.003. Retrieved from https://escholarship.umassmed.edu/oapubs/3986
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This work is licensed under a Creative Commons Attribution 4.0 License.
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