Hydrogen peroxide enhances osteopontin expression and matrix metalloproteinase activity in aortic vascular smooth muscle cells.
1. Restenosis after percutaneous coronary intervention (PCI) is a major clinical complication. However, the underlying mechanisms remain poorly understood. The present aim of the present study was to test the hypothesis that reactive oxygen species (ROS) enhance osteopontin (OPN) expression and increase matrix metalloproteinase (MMP)-2 activity (two major factors that contribute to restenosis) in aortic vascular smooth muscle cells (VSMC), thus facilitating restenosis. 2. Primary cultured rat aortic VSMC were exposed to different concentrations (10, 50 and 100 micromol/L) of H(2)O(2). The expression of OPN mRNA and protein was determined by reverse transcription-polymerase chain reaction and Western blotting, respectively. The activity of MMP-2 was determined by gelatin zymography. 3. The expression of OPN mRNA and protein in VSMC was enhanced by H(2)O(2) in a dose-dependent manner. In addition, H(2)O(2) at all concentrations tested (which are comparable to those seen in diabetic vascular tissues) significantly increased MMP-2 activity in VSMC. 4. Because vascular ROS production is significantly increased in patients with ischaemic disease and OPN and MMP-2 have been shown to play critical role in restenosis, the results of the present study strongly suggest that a ROS-initiated and OPN- and MMP-2-mediated signalling pathway may play an important role in accelerated restenosis after PCI in patients with ischaemic disease. Therefore, the H(2)O(2)-OPN/MMP-2 system may be a new therapeutic target in reducing restenosis in patients undergoing PCI.
Hu
Tao
T
Deparrment of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Luan
Ronghua
R
Zhang
Haifeng
H
Lau
Wayne B
WB
Wang
Qiong
Q
Zhang
Yao
Y
Wang
Hai-Chang
HC
Tao
Ling
L
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D053495:Osteopontin / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology
D017382:Reactive Oxygen Species; D053495:Osteopontin; D006861:Hydrogen Peroxide; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat