Faculty Collaboration Database

Inhibition of matrix metalloproteinase activity by ACE inhibitors prevents left ventricular remodeling in a rat model of heart failure. Am J Physiol Heart Circ Physiol 2007 Jun;292(6):H3057-64

Date

02/20/2007

Pubmed ID

17308006

DOI

10.1152/ajpheart.00447.2006

Scopus ID

2-s2.0-34447507856 (requires institutional sign-in at Scopus site)   63 Citations

Abstract

Angiotensin-converting enzyme (ACE) inhibitors represent the front-line pharmacological treatment of heart failure, which is characterized by left ventricular (LV) dilatation and inappropriate hypertrophy. The mechanism of action of ACE inhibitors is still unclear, but evidence suggests that they may act by influencing matrix metalloproteinase (MMP) activity. This study sought to determine whether ACE inhibitors can directly regulate MMP activity and whether this results in positive structural and functional adaptations to the heart. To this end, MMP-2 activity in LV tissue extracted from rats with an aortocaval (AV) fistula was assessed by in vitro incubation as well as in vivo treatment with captopril, lisinopril, or quinapril. Furthermore, LV size and function were determined in untreated AV fistula rats, AV fistula rats treated with lisinopril (3, 5, and 8 wk), and age-matched sham-operated controls. In vitro incubation with captopril, lisinopril, or quinapril significantly reduced MMP-2 activity, as did in vivo treatment. This occurred without a reduction in the available pool of MMP-2 protein. Long-term in vivo administration of lisinopril also prevented LV dilatation, attenuated myocardial hypertrophy, and prevented changes in myocardial compliance and contractility. The results herein demonstrate that ACE inhibitors prevent MMP-2 activity and, in so doing, represent a mechanism responsible for preventing the negative structural and functional changes that occur in the rat AV fistula model of heart failure.

Author List

Brower GL, Levick SP, Janicki JS

MESH terms used to index this publication - Major topics in bold

Angiotensin-Converting Enzyme Inhibitors
Animals
Aorta
Arteriovenous Shunt, Surgical
Captopril
Compliance
Disease Models, Animal
Heart Failure
Hypertrophy, Left Ventricular
Lisinopril
Male
Matrix Metalloproteinase 2
Matrix Metalloproteinase Inhibitors
Myocardial Contraction
Myocardium
Rats
Rats, Sprague-Dawley
Tetrahydroisoquinolines
Time Factors
Venae Cavae
Ventricular Function, Left
Ventricular Pressure
Ventricular Remodeling