Lysophosphatidylcholine increases the secretion of matrix metalloproteinase 2 through the activation of NADH/NADPH oxidase in cultured aortic endothelial cells

Matrix metalloproteinases (MMPs) play a pivotal role in angiogenesis, ather ogenesis, vascular remodeling after vascular injury, and instability of ath erosclerotic plaque. The present study was undertaken to investigate the ef fect of lysophosphatidylcholine, a major component of oxidized low density lipoprotein (LDL), on the regulation of MMPs in cultured bovine aortic endo thelial cells (BAECs). Furthermore, we explored the potential role of oxida tive stress in the regulation of MMP. LPC increased the secretion of gelati nolytic activity, as well as, protein of MMP-2 from BAECs. The stimulation of BAEC with superoxide increased the production of MMP-2 and it also induc ed its activation. Electron spin resonance (ESR) with 5,5-dimethyl-1-pyrrol ine-N-oxide (DMPO) as spin trap agent demonstrated that lysophosphatidychol ine (LPC) induced generation of reactive oxygen (ROS) species from BAECs. T he inhibition of NADH/NADPH oxidase, one of the potential sources of supero xide in endothelial cells, attenuated the effect of LPC. Our findings sugge st that LPC might activate the endothelial NADH/NADPH oxidase to enhance su peroxide production, and it might, in turn, enhance MMP-2 induction. (C) 20 01 Elsevier Science Ireland Ltd. All rights reserved.