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, atherogenesis, vascular remodeling after vascular injury, and instability of atherosclerotic plaque. The present study was undertaken to investigate the effect of lysophosphatidylcholine, a major component of oxidized low density lipoprotein (LDL), on the regulation of MMPs in cultured bovine aortic endothelial cells (BAECs). Furthermore, we explored the potential role of oxidative stress in the regulation of MMP. LPC increased the secretion of gelatinolytic 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 induced its activation. Electron spin resonance (ESR) with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as spin trap agent demonstrated that lysophosphatidycholine (LPC) induced generation of reactive oxygen (ROS) species from BAECs. The inhibition of NADH/NADPH oxidase, one of the potential sources of superoxide in endothelial cells, attenuated the effect of LPC. Our findings suggest that LPC might activate the endothelial NADH/NADPH oxidase to enhance superoxide production, and it might, in turn, enhance MMP-2 induction.
First Department of Internal Medicine, School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Japan.
N
N
Inoue
S
S
Takeshita
D
D
Gao
T
T
Ishida
S
S
Kawashima
H
H
Akita
R
R
Tawa
H
H
Sakurai
M
M
Yokoyama
D000818:Animals; D001011:Aorta; D015153:Blotting, Western; D002417:Cattle; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000378:metabolism; D004789:Enzyme Activation; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D011233:Precipitin Tests; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000494:pharmacology
D008244:Lysophosphatidylcholines; D017382:Reactive Oxygen Species; D009243:NAD; D013481:Superoxides; D009249:NADP; D019255:NADPH Oxidases; D020778:Matrix Metalloproteinase 2