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KMID : 0191120120270070803
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Journal of Korean Medical Science
2012 Volume.27 No. 7 p.803 ~ p.810
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Impact of Lysophosphatidylcholine on the Plasminogen Activator System in Cultured Vascular Smooth Muscle Cells
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Yoon Byung-Koo
Kang Young-Hee
Oh Won-Jong
Park Kyung-won
Lee Dong-Yun
Choi Doo-Seok
Kim Duk-Kyung
Lee Young-Joo
Rhyu Mee-Ra
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Abstract
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The balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis. PAI-1 expression increases in atherosclerotic arteries and vascular smooth muscle cells (VSMCs) are one of major constituents of atheroma. We investigated the impact of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, on the plasminogen activator system of the rat VSMCs. The lysoPC stimulated the protein and gene expressions of PAI-1 but did not affect the protein expression of t-PA. Fibrin overlay zymography revealed that lysoPC increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA. Vitamin E inhibited the lysoPC-induced PAI-1 expression. Further, lysoPC increased the intracellular reactive oxygen species (ROS) formation. Caffeic acid phenethyl ester, an inhibitor of NF-κB, blocked this lysoPC effect. Indeed, lysoPC induced the NF-κB-mediated transcriptional activity as measured by luciferase reporter assay. In addition, genistein, an inhibitor of protein-tyrosine kinase (PTK), diminished the lysoPC effect, while 7,12-dimethylbenz[a]anthracene, a stimulator of PTK, stimulated PAI-1 production. In conclusion, lysoPC does not affect t-PA expression but induces PAI-1 expression in the VSMC by mediating NF-κB and the genistein-sensitive PTK signaling pathways via oxidative stress. Importantly, lysoPC stimulates the enzyme activity of PAI-1 and suppresses that of t-PA.
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KEYWORD
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Lysophosphatidylcholines, NF-kappa B, Oxidative Stress, Plasminogen Activator Inhibitor 1, Protein-Tyrosine Kinase, Muscle, Smooth, Vascular
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