Original Article

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

Li, Lihua MD^*; Li, Juan PhD^†; Yi, Jing PhD^‡; Liu, Hang MM^§; Lei, Han MD^*

Departments of ^*Cardiology; and

^†Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;

^‡Department of Health Statistics and Information Management, School of Public Health and Management, Chongqing Medical University, Chongqing, China; and

^§Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Reprints: Hang Liu, MM, Department of Urology, The First Affiliated Hospital of Chongqing Medical University, NO.1 Yuanjiagang Youyi road, Yuzhong district, Chongqing 400016, China (e-mail: [email protected]) or Han Lei, MD, Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, NO.1 Yuanjiagang Youyi road, Yuzhong district, Chongqing 400016, China (e-mail: [email protected]).

Supported by Project of Chongqing Medical University (Grant no. XBYB2007013), Doctoral Funding of Chongqing Medical University, and Project of Chongqing Municipal Health Bureau (Grant no. 2009-2-318).

The authors report no conflicts of interest.

Journal of Cardiovascular Pharmacology 71(2):p 82-94, February 2018. | DOI: 10.1097/FJC.0000000000000544

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.