Atorvastatin attenuates plaque vulnerability by downregulation of EMMPRIN expression via COX-2/PGE2 pathway.

Extracellular matrix metalloproteinase inducer (EMMPRIN) reportedly has a key regulatory role in matrix metalloproteinase (MMP) activities and the progression of atherosclerosis. Statins, which are anti-atherosclerotic pharmacological agents, are widely applied in clinical settings. The aim of the present study was to investigate the pharmaceutical effect of atorvastatin on EMMPRIN expression in atherosclerotic plaques. An atherosclerotic mouse model was established using apoliprotein E-deficient (ApoE(-/-)) mice raised on a high-fat diet. Additionally, a low (5 mg/kg/day) or high dosage (10 mg/kg/day) of atorvastatin suspension was administered orally for eight weeks, beginning on week 7 or 11 respectively. The effects of atorvastatin on atherosclerotic plaque formation and EMMPRIN expression were subsequently determined. The THP-1 cell line was used to investigate the effect of atorvastatin on EMMPRIN expression in vitro. The results demonstrated that the high-fat diet led to vulnerable plaques (VPs) and increased EMMPRIN expression in VPs in ApoE(-/-) mice. Atorvastatin treatment decreased EMMPRIN expression in the aortas and plaques of ApoE(-/-) mice. In vitro, oxidized low-density lipoprotein (ox-LDL) induced the expression of cyclooxygenase-2 (COX-2) and EMMPRIN in THP-1 macrophages, and atorvastatin inhibited ox-LDL-induced expression of PGE2, EMMPRIN and COX-2 in THP-1 macrophages. Therefore, the present data indicated that atorvastatin treatment reduces the vulnerability of atherosclerotic plaques and expression of EMMPRIN, and that the inhibitory effect of atorvastatin on EMMPRIN may occur via the COX-2/PGE2 signaling pathway in macrophages.