Dose–Effect of Irbesartan on Cyclooxygenase-2 and Matrix Metalloproteinase-9 Expression in Rabbit Atherosclerosis. Issue 2 (February 2018)

• Record Type: Journal Article
• Authors: Li, Lihua; Li, Juan; Yi, Jing; Liu, Hang; Lei, Han
• Is Part Of: Journal of cardiovascular pharmacology. Volume 71:Issue 2(2018)
• Publication Date: 2018-02
• Subjects: anti-atherosclerosis -- irbesartan -- celecoxib -- cyclooxygenase-2 -- metalloproteinase-9 -- nuclear factor-κB; Cardiovascular Diseases -- drug therapy -- Periodicals; Cardiovascular System -- drug effects -- Periodicals; Cardiovascular pharmacology -- Periodicals; Cardiovascular agents -- Periodicals; Cardiovascular agents; Cardiovascular pharmacology; Periodicals; 615.7105
• DOI: 10.1097/FJC.0000000000000544
• Languages: English
• ISSNs: 0160-2446

Abstract

Abstract : 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 −1 ·day −1 ), medium-dose (20 mg·kg −1 ·d −1 ), and high-dose (30 mg·kg −1 ·d −1 ) irbesartan and celecoxib (20 mg·kg −1 ·d −1 ). 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.