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

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.