Effect of Angiotensin II on Matrix Metalloproteinase-2 Secretion in Human Umbilical Vein Endothelial Cells.

Abstract

Matrix metalloproteinase (MMP), which is secreted from vascular cells, is an enzyme-degrading extracellular matrix protein. MMP molecules, including MMP-2, are involved in the destabilization of atherosclerotic plaque and plaque rupture during the development of cardiovascular disease. Angiotensin II (Ang-II), a vascular stimulant associated with cardiovascular disease progression, has been demonstrated to be mainly involved in cardiovascular remodeling of atherosclerosis and cardiac hypertrophy. This study was performed to investigate the regulation of MMP-2 by Ang-II in human umbilical vein endothelial cells (HUVECs). Ang-II significantly increased MMP-2 secretion and MMP-2 messenger RNA expression in HUVECs. The effects of Ang-II were suppressed by the coexistence of telmisartan, a blocker of the Ang-II receptor type 1 (AT1 receptor), or PD123319, a blocker of Ang-II receptor type 2 (AT2 receptor). Especially, PD123319 showed marked suppression of the effect of Ang-II on MMP-2. Therefore, Ang-II-induced upregulation of MMP-2 in HUVECs was considered to be mainly achieved through AT2 receptors, although AT1 and AT2 receptors were expressed in HUVECs, but the detailed mechanisms remain undefined. These findings suggest that Ang-II can enhance MMP-2 mainly through AT2 receptors in endothelial cells, but the significance of circulating MMP-2 as a cardiovascular biomarker requires confirmation in further clinical studies.