MicroRNA363-5p Targets Thrombospondin3 to Regulate Pathological Cardiac Remodeling

Abstract Cardiac remodeling is an end-stage manifestation of multiple cardiovascular diseases, and microRNAs are involved in a variety of posttranscriptional regulatory processes. miR-363-5p targeting of Thrombospondin3 (THBS3) has been shown to play an important regulatory role in vascular endothelial cells, but the roles of these two in cardiac remodeling are unknown. We first established an in vivo model of cardiac remodeling induced by transverse aortic narrow (TAC). human cardiomyocyte cell line (AC16) and human cardiac fibroblast cell line (HCF) were treated with 1 µmol/L angiotensin II (AngⅡ) to construct an in vitro model of myocardial hypertrophy and myocardial fibrosis. In all three of the above models, we found a significant decreasing trend of miR-363-5p, suggesting that it plays a key regulatory role in the occurrence and development of cardiac remodeling. Subsequently, overexpression of miR-363-5p significantly attenuated myocardial hypertrophy and myocardial fibrosis in vitro as evidenced by reduced the area of AC16, the cell viability of HCFs, the relative expression of the protein of fetal genes (ANP, BNP, β-MHC) and fibrosis marker (collagen Ⅰ, collagen Ⅲ, α-MSA), whereas inhibition of miR-363 -5p expression showed the opposite trend. In addition, we also confirmed the targeted binding relationship between miR-363-5p and THBS3 by dual luciferase reporter gene assay, and the relative expression of THBS3 mRNA and protein were significantly decreased upon overexpression of miR-363-5p. Moreover, overexpression of miR-363-5p with THBS3 Simultaneously partially eliminated the delaying effect of miR-363-5p on myocardial hypertrophy and myocardial fibrosis in vitro. In conclusion, Overexpression of miR-363-5p attenuated the prohypertrophic and profibrotic effects of Ang II on AC16 and HCF by a mechanism related to the inhibition of THBS3 expression.