Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that have shown promise as noninvasive biomarkers in cardiac disease. This study was undertaken to investigate the miRNA expression profile in dogs with myxomatous mitral valve disease (MMVD). 277 miRNAs were quantified using RT-qPCR from six normal dogs (American College of Veterinary Internal Medicine Stage A), six dogs with MMVD mild to moderate cardiac enlargement (ACVIM Stage B1/B2) and six dogs with MMVD and congestive heart failure (ACVIM Stage C/D). Eleven miRNAs were differentially expressed (False Discovery Rate < 0.05). Dogs in Stage B1/B2 or C/D had four upregulated miRNAs, including three cfa-let-7/cfa-miR-98 family members, while seven others were downregulated, compared to Stage A. Expression of six of the 11 miRNAs also were significantly different between dogs in Stage C/D and those in Stage B1/B2. The expression changes were greater as disease severity increased. These miRNAs may be candidates for novel biomarkers and may provide insights into genetic regulatory pathways in canine MMVD.
Highlights
MicroRNAs are small (~22 nucleotide) single-stranded non-coding RNA molecules that negatively regulate gene expression by promoting degradation of mRNA transcripts or inhibition of protein translation [1]
Myxomatous mitral valve disease (MMVD) affects approximately 9% of all dogs, increasing with age such that the overall cumulative incidence is greater than 40% [4,5]
All 11 of these differed between MMVD Stage A and Stage C/D, while nine differed between Stage A and Stage B1/B2
Summary
MicroRNAs (miRNAs) are small (~22 nucleotide) single-stranded non-coding RNA molecules that negatively regulate gene expression by promoting degradation of mRNA transcripts or inhibition of protein translation [1]. Even though miR-499 is expressed almost exclusively in heart tissue, plasma miR-499 concentrations were significantly elevated in human patients with myocardial infarction compared with other groups of patients [17] These findings suggest that circulating biomarkers can serve as appropriate surrogates for the heart tissues in the study of cardiac disease [18]. In a most recent study, Zhang et al reported 16 miRNAs differentially expressed between the control dogs and dogs with atrial fibrillation and proposed a novel role of cfa-miR-206 in canine atrial fibrillation [22] Despite this progress, more research is urgently needed to advance our understanding of the role of miRNAs in canine cardiac disease and CHF
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