Journal
INTERNATIONAL JOURNAL OF CARDIOLOGY
Volume 184, Issue -, Pages 190-197Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.ijcard.2015.01.075
Keywords
microRNA; RNA sequencing; Transcriptomic study; Paroxysmal atrial fibrillation
Categories
Funding
- American Heart Association [12PRE11700012, 13EIA14560061, 14SDG20080008]
- NIH [HL089598, HL091947, HL117641, HL118761]
- Fondation Leducq networks 'European North-American Atrial Fibrillation Research Alliance' [ENAFRA: 07CVD03]
- European Network for Translational Research in Atrial Fibrillation [EUTRAF: 261057]
- Transatlantic Networks of Excellence in Cardiovascular Research [14CVD01]
- Vivian L. Smith Foundation
- Juanita P. Quigley endowed chair in cardiology
- Baylor College of Medicine Medical Scientist Training Program Caskey Scholarship
Ask authors/readers for more resources
Background: The molecular mechanisms underlying the early development of atrial fibrillation (AF) remain poorly understood. Emerging evidence suggests that abnormal epigenetic modulation via microRNAs (miRNAs) might be involved in the pathogenesis of paroxysmal AF (pAF). Objective: To identify key molecular changes associated with pAF, we conducted state-of-the-art transcriptomic studies to identify the abnormal miRNA-mRNA interactions potentially driving AF development. Methods: High-quality total RNA including miRNA was isolated from atrial biopsies of age-matched and sex-matched pAF patients and control patients in sinus rhythm (SR; n = 4 per group) and used for RNA-sequencing and miRNA microarray. Results were analyzed bioinformatically and validated using quantitative real-time (qRT)-PCR and 3'UTR luciferase reporter assays. Results: 113 genes and 49 miRNAs were differentially expressed (DE) in pAF versus SR patients. Gene ontology analysis revealed that most of the DE genes were involved in the gonadotropin releasing hormone receptor pathway and p53 pathway. Of these DE genes, bioinformatic analyses identified 23 pairs of putative miRNA-mRNA interactions that were altered in pAF (involving 15 miRNAs and 17 mRNAs). Using qRT-PCR and 3'UTR luciferase reporter assays, the interaction between upregulation ofmiR-199a-5p and downregulation of FKBP5 was confirmed in samples from pAF patients. Conclusion: Our combined transcriptomic analysis and miRNA microarray study of atrial samples from pAF patients revealed novel pathways and miRNA-mRNA regulations that may be relevant in the development of pAF. Future studies are required to investigate the potential involvement of the gonadotropin releasing hormone receptor and p53 pathways in AF pathogenesis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available