Angiotensin II induces matrix metalloproteinase-9 expression via a nuclear factor-kappaB-dependent pathway in vascular smooth muscle cells

Angiotensin II (AngII) is widely recognized as a critical regulator of the development of atherosclerosis. Matrix metalloproteinases (MMPs) are thought to participate in plaque destabilization through degradation of the extracellular matrix. In the present study, we investigated the potential mechanism of AngII-induced MMP-9 expression in vascular smooth muscle cells (VSMC). AngII upregulated the expression of MMP-9 significantly in VSMC obtained from rat aorta. RNAi-mediated knockdown of p65 and losartan, an inhibitor of AngII receptors subtype-1 (AT(1)), could abolish AngII-induced MMP-9 expression. In addition, AngII induced the NF-kappa B binding activity via AT(1) and AT(2) receptors in VSMC, and AngII-induced activation of NF-kappa B is not associated with significant downregulation of I kappa B. In summary, this study demonstrates that AngII stimulates NF-kappa B nuclear translocation in VSMC via AT(1) and AT(2). AngII increases the expression of MMP-9 in VSMC, and AT(1) and NF-kappa B pathways have an important role in this response. (C) 2008 Elsevier B.V. All rights reserved.