Angiotensin II, the main component of the renin-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 the pivotal participation of these cells in pathological cardiovascular remodeling mediated by
angiotensin II.