Dose-Effect of Irbesartan on Cyclooxygenase-2 and Matrix Metalloproteinase-9 Expression in Rabbit Atherosclerosis

Abstract

Irbesartan has previously shown antiatherosclerotic effects on human carotid atherosclerotic plaques. Our study aimed to assess the dose-effect of irbesartan on cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) in rabbit atherosclerotic aorta. New Zealand rabbits were randomly divided into 6 groups: normal control (NC), high cholesterol (HC), low-dose (10 mg·kg·day), medium-dose (20 mg·kg·d), and high-dose (30 mg·kg·d) irbesartan and celecoxib (20 mg·kg·d). Except for the NCs, rabbits were fed a HC diet for 14 weeks to induce atherosclerosis. Aortic atherosclerotic lesions and messenger RNA and protein expression of COX-2, MMP-9, and nuclear factor-κB (NF-κB) were subsequently measured. The surface area of aortic atherosclerotic lesions was visibly larger in the HC group than in NCs (P < 0.01), but showed considerable reduction with medium- and high-dosage irbesartan and celecoxib treatments (P < 0.01). In medium- and high-dosage irbesartan and celecoxib groups, COX-2 and MMP-9 expression and NF-κB activity were significantly lower than in the high-cholesterol group (P < 0.01). No significant differences in treatment effects were observed between the high-dosage irbesartan and celecoxib groups (P > 0.05). Our results indicate that medium and high doses of irbesartan and celecoxib have antiatherosclerotic effects in aortic plaques via inhibition of COX-2 and MMP-9 by suppressing NF-κB activation. High-dose irbesartan has effects similar to celecoxib.