Division of Cardiovascular Medicine, Department of Medicine; Department of Quantitative Health Sciences; Graduate School of Biomedical Sciences
Biological Factors | Cardiology | Cardiovascular Diseases | Nucleic Acids, Nucleotides, and Nucleosides | Pathological Conditions, Signs and Symptoms | Tissues
Introduction: Epicardial adipose tissue (EAT) has been linked to incidence and recurrence of atrial fibrillation (AF), but the underlying mechanisms that mediate this association remain unclear. Circulating microRNAs (miRNAs) contribute to the regulation of gene expression in cardiovascular diseases, including AF. Thus, we sought to test the hypothesis that circulating miRNAs relate to burden of EAT.
Methods: We examined the plasma miRNA profiles of 91 participants from the miRhythm study, an ongoing study examining associations between miRNA and AF. We quantified plasma expression of 86 unique miRNAs commonly expressed in cardiomyocytes using quantitative reverse transcriptase polymerase chain reaction (qPCR). From computed tomography, we used validated methods to quantify the EAT area surrounding the left atrium (LA) and indexed it to body surface area (BSA) to calculate indexed LA EAT (iLAEAT). Participants were divided into tertiles of iLAEAT to identify associations with unique miRNAs. We performed logistic regression analyses adjusting for factors associated with AF to examine relations between iLAEAT and miRNA. We performed further bioinformatics analysis of miRNA predicted target genes to identify potential molecular pathways are regulated by the miRNAs.
Results: The mean age of the participants was 59 +/- 9, 35% were women, and 97% were Caucasian. Participants in the highest tertile of iLAEAT were more likely to have hypertension, heart failure, and thick posterior walls. In regression analyses, we found that miRNAs 155-5p (p < 0.001) and 302a-3p (p < 0.001) were significantly associated with iLAEAT in patients with AF. The predicted targets of the miRNAs identified were implicated in the regulation of cardiac hypertrophy, adipogenesis, interleukin-8 (IL-8), and nerve growth factor (NGF) signaling.
Conclusion: miRNA as well as EAT have previously been linked to AF. Our finding that iLAEAT and miRNAs 155-5p and 302a-3p are associated suggest a possible direct link to between these entities in the development and maintenance of AF. Further research is needed to study causal relationships between these biomarkers.
atrial fibrillation, cardiac remodeling, epicardial adipose tissue, inflammation, microRNA
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Copyright © 2019 Tran, Majka, Sanghai, Sardana, Lessard, Milstone, Tanriverdi, Freedman, Fitzgibbons and McManus. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
DOI of Published Version
Front Cardiovasc Med. 2019 Aug 14;6:115. doi: 10.3389/fcvm.2019.00115. eCollection 2019. Link to article on publisher's site
Frontiers in cardiovascular medicine
Tran, Khanh-Van T.; Majka, Jordan; Sanghai, Saket; Sardana, Mayank; Lessard, Darleen M.; Milstone, Zachary J.; Tanriverdi, Kahraman; Freedman, Jane E.; Fitzgibbons, Timothy P.; and McManus, David D., "Micro-RNAs Are Related to Epicardial Adipose Tissue in Participants With Atrial Fibrillation: Data From the MiRhythm Study" (2019). Open Access Articles. 3945.
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