Recombinant Matrix Metalloproteinase-9 Induces Ventricular Remodeling By Up-Regulating Angiotensin II

Abstract

Abstract Objective To study the effect of matrix metalloproteinase-9 (MMP-9) on ventricular remodeling and involvement of angiotensin II (Ang II). Methods Thirty-six adult male Wistar rats were randomly divided into control (n = 12), MMP-9 (n = 12), and MMP-9 + olmesartan (n = 12) groups. Recombinant MMP-9 (2.1 ng/g) was injected intraperitoneally twice a week. Olmesartan (3 mg/kg) was given by oral gavage once daily. Animals were treated for 4 or 8 weeks. Cardiac function was assessed by echocardiography followed by histological analysis. The messenger RNA (mRNA) and protein levels of MMP-9 in myocardial tissues were analyzed by reverse transcription polymerase chain reaction and Western blotting, respectively. Serum levels of Ang I, II, angiotensin converting enzyme (ACE) and MMP-9 were determined by enzyme-linked immunosorbent assay (ELISA). Results MMP9 administration for 4 or 8 weeks increased mRNA and protein levels of MMP-9 in myocardial tissues, serum levels of MMP-9, Ang I, II and ACE, and left ventricular mass index (LVMI) but decreased collagen volume fraction (CVF) compared with the control group (all P < 0.05). Cardiomyocyte cell size was significantly enlarged and disorganized with cytoplasmic lysis and necrosis in the MMP-9 group. After olmesartan treatment, myocardial MMP-9 mRNA and protein levels, serum levels of MMP-9 and Ang II, and LVMI were lower, and CVF was higher with significant improvement in myocardial morphology and cardiac function (all P<0.05). Conclusion Recombinant MMP-9 treatment induces ventricular remodeling and cardiac dysfunction by up-regulating Ang II.