Effect of carvedilol on cardiac metalloproteinases and tissue inhibitors of metalloproteinases after myocardial infarction in rats
10.3724/SP.J.1008.2008.00380
- Author:
Jing-Ming YI
1
Author Information
1. Department of Cardiovasology
- Publication Type:Journal Article
- Keywords:
Carvedilol;
Matrix metalloproteinases;
Myocardial infarction;
Tissue inhibitors of metalloproteinases
- From:
Academic Journal of Second Military Medical University
2010;29(4):380-385
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effect of carvedilol on expression of cardiac matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) after myocardial infarction in rats. Methods: An animal model of acute myocardial infarction (AMI) was established by descending left coronary artery ligation in 24 rats and they were divided into carvedilol (10 mg • kg-1 • d-1) group (n=12) and normal saline group (n=12). Sham-operated group (n=9) received the same procedure but with no ligation. All animals were treated for 6 weeks via a gastric lavage. Heart function and hemodynamic parameters were determined after 6 weeks. The protein expression of cardiac MMP-2, MMP-9 and TIMP-2 was detected by immunohistochemical analysis in AMI groups, and the MMPs activities were assessed by zymography. Gene expression of myocardial MMPs/TIMPs (MMP-2,-9 and TIMP-1, -2) and cytokines (TNF-α, IL-1β) were measured by real-time quantitative PCR. Results: Compared with Sham-operated group, carvedilol group had significantly higher left ventricular end-diastolic pressure (LV-EDP) and lower LV upstroke velocity (+dp/dtmax) and LV descent velocity (- dp/dtmax) (P<0.01). Activities of MMP-2 and MMP-9, protein expression of MMP-2, MMP-9 and TIMP-2, and mRNA expression of MMP-2, MMP-9, TIMP-1, TIMP-2, IL-1β, and TNF-α were all higher in carvedilol group compared with sham-operated group (P<0.05). Compared with normal saline group, carvedilol group had lower LVEDP(P
