Lysophosphatidylcholine Potentiates the Mitogenic Effect of Various Vasoactive Compounds on Rabbit Aortic Smooth Muscle Cells.
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概要
- 論文の詳細を見る
We examined the mechanism of action of lysophosphatidylcholine (lyso-PC), which is suggested to be involved in the pathogenesis of atherosclerosis and inflamatory disorders, and its interaction with well-known vasoactive compounds such as hydrogen peroxide (H2O 2), thromboxane A2 (TX-A2), serotonin (5-HT), angiotensin II (Ang-II), endothelin-1 (ET-1), or urotensin II (U-II) on VSMC proliferation. Growth-arrested rabbit VSMCs were incubated with given concentrations of lyso-PC with H2O2, TX-A2, 5-HT, Ang-II, ET-1, or U-II. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. Lyso-PC induced a maximal effect on [3H]thymidine incorporation at a concentration of 15 μM (156%), and its effect was significantly inhibited by the phospholipase C inhibitor U73122 (10 μM), the intracellular antioxidant NAC (400 μM), and the NADPH oxidase inhibitor diphenylene iodonium (1 μM), but not by the MAPK kinase inhibitor (10 μM). H2O2, TX-A2, 5-HT, Ang-II, ET-1, or U-II also stimulated [3H]thymidine incorporation in a dose-dependent manner. A non-mitogenic concentration of lyso-PC (5 μM) significantly potentiated the effect of low concentrations of H2O2 (0.1 μM, 110 to 222%), TX-A2 (5 μM, 120 to 202%), 5-HT (5 μM, 182 to 259%), Ang-II (0.5 μM, 167 to 304%), ET-1 (0.01 μM, 139 to 297%), or U-II (0.025 μM, 120 to 332%) on [3H]thymidine incorporation. The results suggest that lyso-PC acts synergistically with the vasoactive compounds H2O2, TX-A2, 5-HT, Ang-II, ET-1, or U-II in inducing VSMC proliferation, which may play an important role in the progression of atherosclerosis.
- International Heart Journal刊行会の論文
著者
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Koba Shinji
The Third Department Of Internal Medicine School Of Medicine Showa University
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Benedict Claude
Department Of Internal Medicine University Of Texas-houston Health Science Center
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Watanabe Takuya
The Third Department of Internal Medicine
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Pakala Rajbabu
Department of Internal Medicine, Division of Cardiology, Univeristy of Texas-Houston Health Science
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Katagiri Takashi
The Third Department Of Internal Medicine Showa University
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