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Inhibition of matrix metalloproteinase activity in the myocardium by ACE inhibitors
Author(s) -
Levick Scott P,
Brower Gregory L,
Chastain Ashley M,
Bertling Michelle L,
Janicki Joseph S
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a762-c
Subject(s) - lisinopril , quinapril , captopril , in vivo , medicine , heart failure , ace inhibitor , matrix metalloproteinase , muscle hypertrophy , cardiology , pharmacology , angiotensin converting enzyme , endocrinology , biology , blood pressure , microbiology and biotechnology
Angiotensin converting enzyme (ACE) inhibitors represent the front line pharmacological treatment for heart failure, 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 influence 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. MMP activity in LV tissue extracted from rats one day after the creation of an aortocaval (AV) fistula was assessed by in vitro incubation with captopril, lisinopril or quinapril. Further, LV size and function were determined in AV fistula rats treated with lisinopril for 3, 5 and 8 weeks. In vitro incubation and in vivo treatment with captopril, lisinopril or quinapril significantly reduced MMP activity. 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 activation of MMPs, and in so doing identify a novel mechanism responsible for preventing the negative structural and functional changes that occur in the rat AV fistula model of heart failure. This study was supported in part by NIH R01‐HL62228 (JSJ), R01‐ HL073990 (JSJ)