Effects of atorvastatin on expression of ICAM-1 in atherosclerotic rabbits.

Abstract

AIMS: Lipid accumulation and inflammatory response are major events in the progression of atherosclerosis. This research was performed to determine if atorvastatin could prevent atherosclerosis and its underlying mechanisms. METHODS: An atherosclerotic model was established in rabbits. Atorvastatin was administrated by gavage. Blood samples were collected to measure plasma total cholesterol, total triglyceride and low-density lipoprotein (LDL)-cholesterol. After the high-cholesterol diet with or without atorvastatin treatment, the morphological changes of the rabbits were examined with hematoxylin and eosin staining of tissues, and the expression of intercellular adhesion molecule 1 (ICAM-1) was determined by immuno-staining and reverse transcriptase-PCR (RT-PCR). RESULTS: Atorvastatin significantly reduced plasma levels of total cholesterol (41.7%) and LDL-cholesterol (34.6%). Neither the hypercholesterol diet nor atorvastatin treatment had any significant impact on body weight and plasma triglycerides. Treatment with atorvastatin significantly restored 40.9% of the widened intima and even down-regulated the ratio of intima/media by 55.5%. The inhibitory effects of atorvastatin on the expression of ICAM-1 showed a decrease of up to 37.6% (P < 0.01). The diseased rabbits showed a 167.3% increase in ICAM-1 mRNA expression (P < 0.01), which was reversed by nearly 46.4% by treatment with atorvastatin. CONCLUSION: Atorvastatin significantly prevents atherosclerotic changes in rabbits with a high-cholesterol diet, possibly by lowering plasma lipids and decreasing over-expressed ICAM-1.