Abstract
This study aimed to identify the expression profile of circulating microRNAs in dogs with eccentric or concentric cardiac hypertrophy. A total of 291 microRNAs in serum samples of five dogs with myxomatous mitral valve degeneration (MMVD) and five dogs with pulmonic stenosis (PS) were compared with those of five healthy dogs using microarray analysis. Results of microarray analysis revealed up-regulation of cfa-miR-130b [fold change (FC) = 2.13, p = 0.014), down-regulation of cfa-miR-375 (FC = 1.51, p = 0.014), cfa-miR-425 (FC = 2.56, p = 0.045), cfa-miR-30d (FC = 3.02, p = 0.047), cfa-miR-151 (FC = 1.89, p = 0.023), cfa-miR-19b (FC = 3.01, p = 0.008), and cfa-let-7g (FC = 2.53, p = 0.015) in MMVD group which showed eccentric cardiac hypertrophy, up-regulation of cfa-miR-346 (FC = 2.74, p = 0.032), down-regulation of cfa-miR-505 (FC = 1.56, p = 0.016) in PS group which showed concentric cardiac hypertrophy, and down-regulation of cfa-miR-30c (FC = 3.45, p = 0.013 in MMVD group; FC = 3.31, p = 0.014 in PS group) and cfa-let-7b (FC = 11.42, p = 0.049 in MMVD group; FC = 5.88, p = 0.01 in PS group) in both MMVD and PS groups. In addition, the unsupervised hierarchical clustering of differentially expressed microRNAs in each group resulted in complete separation of healthy dogs from dogs with heart diseases. Therefore, eleven microRNAs among 291 microRNAs were identified as differentially expressed circulating microRNAs related to MMVD or PS in dogs. This pilot study demonstrates that the microRNAs identified in this study could be possible candidates for novel biomarker or therapeutic target related to cardiac hypertrophy in dogs.
Highlights
Cardiac hypertrophy is an enlargement of the heart, which occurs in response to increased cardiac workload caused by various heart diseases [1]
The breed of dogs included in this study were five Beagle in healthy group, four Maltese and one Shih Tzu in myxomatous mitral valve degeneration (MMVD) group, and two Pomeranian, one French Bulldog, one Mixed-breed, and one Poodle in pulmonic stenosis (PS) group
The LVIDDN was significantly different between the three groups (p = 0.002), the highest in MMVD group and the lowest in PS group
Summary
Cardiac hypertrophy is an enlargement of the heart, which occurs in response to increased cardiac workload caused by various heart diseases [1]. The eccentric cardiac hypertrophy is caused by volume overload diseases such as myxomatous mitral valve degeneration (MMVD), patent ductus arteriosus, and dilated cardiomyopathy in dogs, and results in increased myocyte length and dilated chambers with variable relative wall thickness (RWT) [2]. The concentric cardiac hypertrophy is caused by pressure overload diseases such as pulmonic stenosis (PS) and aortic stenosis in dogs, and results in increased myocyte width and RWT with normal to decreased chamber volume [2]. Significant dysregulations of circulating microRNAs in cardiovascular diseases have been reported [5], and the role of microRNAs in cardiac hypertrophy has been identified [6,7,8]. The microRNAs related to cardiac hypertrophy are increasingly considered as potential therapeutic targets for various heart diseases [9]
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