Tanshinone IIA attenuates atherosclerosis in ApoE-/- mice through down-regulation of scavenger receptor expression

This study is designed to investigate the protection of tanshinone IIA (TSIIA) against atherosclerosis in apolipoprotein E deficient (ApoE(-/-)) mice and to explore the mechanisms by focusing on the expressions of scavenger receptors scavenger receptor-A (SR-A) and CD36 The in vivo study demonstrated that TSIIA (10-90 mg/kg) inhibited the atherosclerotic lesions down regulated the CD68 protein expression in lesion and decreased the contents of cholesterol in aortas of ApoE(-/-) mice In addition TSIIA reduced the serum tern Is of oxidized LDL (oxLDL) and down-regulated the mRNA expression of CD36 SR A and peroxisome proliferator-activated receptor gamma (PPAR gamma) in aortas The in vitro study showed that TSIIA (01-10 mu M) decreased cholesterol level and Dil-oxLDL uptake in mouse peritoneal macrophages treated with oxLDL (50 mu g/ml) In addition TSIIA down-regulated the mRNA and protein expression of CD36 but not that of SR-A in oxLDL treated macrophages TSIIA also down regulated the mRNA expression of PPAR gamma in oxLDL treated macrophages Furthermore TSIIA reduced the mRNA expression of CD36 in macrophages treated with PPAR gamma agonist 15d-PGJ(2) (2 mu M) or troglitazone (50 mu M whereas both 15d PGJ(2) (05- 1 5 mu M and troglitazone (5-20 mu M) dose-dependently abolished the down-regulation of CD36 expression by TSIIA in oxLDL treated macrophages These results suggest that TSIIA attenuates the atherosclerotic lesion in Apol(-/-) mice which might be attributed to the properties of both anti-oxidation and down-regulation of scavenger receptors Furthermore antagonism of PPAR gamma might be involved in the down-regulation of CD36 by TSIIA (C) 2010 Elsevier B V All rights reserved