MicroRNA-98 regulates foam cell formation and lipid accumulation through repression of LOX-1

OBJECTIVE: Several miR/s that regulate gene/s relevant in atherogenesis are being described. We identified a miR (miR-98) that targets LOX-1, a receptor for ox-LDL, and speculated that it might be relevant in atherogenesis. APPROACH AND RESULTS: MicroRNA-98 was predicted by bioinformatics tools. The effects of miR-98 (by use of mimics and inhibitors) on LOX-1 expression and foam cell formation in mouse peritoneal macrophages were assessed. ApoE(-/-) mice fed by high fat diet were administered with mmu-agomiR-98 and mmu-antagomiR-98, and expression of LOX-1 and foam cell formation in aorta were quantified. LOX-1 was established to be a direct target of miR-98 by luciferase reporter assay. Enhancement of miR-98 decreased the expression of LOX-1 and inhibited foam cell formation and lipid accumulation. Inhibition of miR-98 had the opposite effects on all parameters. CONCLUSIONS: Reduced expression of miR-98 may relate to LOX-1 expression and foam cell formation and lipid accumulation in aortas of ApoE(-/-) mice. Plasma level of miR-98 may be a biomarker of atherosclerotic disease process and its modulation may offer a therapeutic strategy for atherosclerosis.