Abstract
Background: Previous studies in humans have confirmed dysregulations of circulating microRNAs (miRNAs) in patients with various cardiovascular diseases. However, studies on circulating miRNAs in dogs with various heart diseases are limited in number. This study aimed to identify significantly dysregulated circulating miRNAs and characterize them as novel biomarkers in dogs with heart diseases.Materials and Methods: Circulating levels of 11 miRNAs were investigated in serum samples of 82 dogs (72 with heart diseases and 10 healthy dogs) using quantitative reverse transcription-polymerase chain reaction. The results were correlated to clinical data including echocardiographic results and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels.Results: Upregulation of cfa-miR-130b was observed in dogs with myxomatous mitral valve degeneration (MMVD) stage B, patent ductus arteriosus, and pulmonic stenosis. In dogs with MMVD stage B, cfa-miR-130b was upregulated and correlated with clinical indices. In receiver operating characteristic (ROC) analysis, cfa-miR-130b accurately distinguished dogs with diseases from healthy dogs. We also observed that cfa-miR-375 and cfa-let-7b were upregulated in dogs with concentric cardiac hypertrophy. The cfa-miR-375 was correlated with concentric hypertrophy indices and was an accurate indicator of concentric hypertrophy in ROC analysis.Conclusions: The miRNAs identified in this study may be used as novel biomarkers and possible candidates for therapeutic targets in various canine heart diseases.
Highlights
MicroRNAs are small, non-coding single-stranded RNAs consisting of 19–24 nucleotides, which form complementary pairs with target mRNAs to inhibit and regulate their expression through translation inhibition or degradation [1]
This study aimed to identify significantly dysregulated circulating miRNAs and evaluate them as novel biomarkers in dogs with various heart diseases, and investigate and characterize circulating miRNAs associated with specific cardiac hypertrophy type
The classification by disease type included 73 dogs consisting of 10 healthy dogs, 35 dogs with myxomatous mitral valve degeneration (MMVD), 21 dogs with patent ductus arteriosus (PDA), and seven dogs with pulmonic stenosis (PS)
Summary
MicroRNAs (miRNA) are small, non-coding single-stranded RNAs consisting of 19–24 nucleotides, which form complementary pairs with target mRNAs to inhibit and regulate their expression through translation inhibition or degradation [1]. Circulating MicroRNAs in Heart Diseases [4,5,6], and circulating miRNAs are increasingly investigated as novel biomarkers in heart diseases because of its stability in peripheral blood [7]. Little is known about expressions and role of circulating miRNAs in dogs with naturally occurring heart diseases. There have been no studies in dogs that have evaluated and characterized the dysregulated miRNAs as novel biomarkers or candidate for therapeutic targets through further analysis with clinical data. Previous studies in humans have confirmed dysregulations of circulating microRNAs (miRNAs) in patients with various cardiovascular diseases. This study aimed to identify significantly dysregulated circulating miRNAs and characterize them as novel biomarkers in dogs with heart diseases
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