Angiotensin II upregulates expressions of matrix metaIloproteinase-2 and tissue inhibitors of metalloproteinase-1 in cardiomyocytes

AIM:To investigate the effect of angiotensin II (AngII) on the expressions of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinase-1 (TIMP-1). METHODS: Cultured cardiomycytes were pretreated with AngII. The level of malonaldehyde (MDA) and enzyme activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were detected by commercial kits. The mRNA and protein expressions of MMP-2 and TIMP-1 in cardiomyocytes were analyzed by qRT-PCR and Western blot. The rat hypertension model was established and the levels of MDA in the heart tissue of model rats and valsartan-treated rats were detected along with the enzyme activity of GPx and SOD. Expressions of MMP-2 and TIMP-1 were also analyzed by qRT-PCR and Western blot. RESULTS: Pretreatment with AngII significantly increased the oxidative stress in myocardial cells and also induced the upregulation of the expressions of MMP-2 and TIMP-1. In hypertensive rats, the oxidative stress in myocardial tissue was significantly higher than that in sham group, but the stress decreased after valsartan treatment. Valsartan also reduced the expressions of MMP-2 and TIMP-1 gene in myocardial tissue of hypertensive rats. CONCLUSION: Oxidative stress increase via AngII is involved in the regulation of MMP-2 and TIMP-1 expression. The mechanism deserves further research.