ABSTRACT
MicroRNAs (miRNAs) have recently attracted increasing attention for their involvement in atherosclerosis (AS). The purpose of this study was to further explore the function and underlying mechanism of miR-135a in AS progression. The expression levels of miR-135a and lipoprotein lipase (LPL) mRNA were detected by qRT-PCR, and LPL protein expression was measured by western blotting. The levels of blood lipids and inflammatory cytokines, and LPL activity were assessed using corresponding Assay Kits, and an HPLC assay was used to determine the levels of free cholesterol (FC), total cholesterol (TC) and cholesterol ester (CE). A Dil-oxLDL binding assay was performed to evaluate the ability of cholesterol uptake. The direct interaction between miR-135a and LPL was confirmed by a dual-luciferase reporter assay and RNA immunoprecipitation assay. Our data indicated that miR-135a was downregulated in serum samples of AS patients and mice. Upregulation of miR-135a alleviated lipid metabolic disorders and inflammation in AS mice. Moreover, miR-135a negatively regulated lipid accumulation and inflammation in ox-LDL-treated THP-1 macrophages. Mechanistically, miR-135a directly targeted LPL and repressed LPL expression. LPL mediated the regulatory effect of miR-135a on lipid accumulation and inflammation in ox-LDL-treated THP-1 macrophages. In conclusion, our study indicated that miR-135a upregulation ameliorated lipid accumulation and inflammation at least partly by targeting LPL in THP-1 macrophages, highlighting miR-135a as a potential antiatherogenic agent.
