RESUMO
Angiotensin II, the main component of the rennin-angiotensin system, is associated with cardiovascular diseases such as hypertension, vascular remodeling and inflammation. Remodeling process results from dysregulation of Matrix Metalloproteinases [MMPs] and their tissue inhibitors [TIMPs]. MMPs are considered as important target genes for angiotensin II. The aim of this study was to determine the effects of angiotensin II on MMP-9 and TIMP-1 production and MMP/TIMP balance in a monocytic cell type. Human monocytic U-937 cells were cultured and treated with 100 nM angiotensin II. Supernatants were analyzed for MMP-9 and TIMP-1 using ELISA and zymography methods. Real-time PCR was utilized to evaluate relative MMP-9 and TIMP-1 genes expression following treatments. Cytotoxicity potentials of treatments were determined by assaying lactate dehydrogenase leakage from the cells. Stimulation of the monocytic cells with angiotensin II significantly increased MMP-9 and TIMP-1 secretion as measured by ELISA [p<0.05]. It also augmented gelatinolytic activity of MMP-9 in the conditioned media as much as 49% [p<0.05]. Incubation of the cells with angiotensin II for 12 hr increased MMP-9 and TIMP-1 gene expression 2.7 and 1.8 folds, respectively [p<0.05]. Angiotensin II treatments did not establish significant cytotoxic effects. In summary, our data provide further evidences that monocytic MMP-9 is a major effector of angiotensin II. It is induced more efficiently than TIMP-1 by angiotensin II that leads to MMP/TIMP imbalance. Our data also reveal by the pivotal participation of these cells in pathological cardiovascular remodeling mediated by angiotensin II