Lysophosphatidylcholine Potentiates the Mitogenic Effect of Various Vasoactive Compounds on Rabbit Aortic Smooth Muscle Cells

Takuya Watanabe, Shinji Koba, Takashi Katagiri, Rajbabu Pakala, Claude R. Benedict
2002 Japanese Heart Journal  
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 (H 2 O 2 ), thromboxane A 2 (TX-A 2 ), 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 H 2 O 2
more » ... , TX-A 2 , 5-HT, Ang-II, ET-1, or U-II. [ 3 H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. Lyso-PC induced a maximal effect on [ 3 H]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). H 2 O 2 , TX-A 2 , 5-HT, Ang-II, ET-1, or U-II also stimulated [ 3 H]thymidine incorporation in a dose-dependent manner. A non-mitogenic concentration of lyso-PC (5 µM) significantly potentiated the effect of low concentrations of H 2 O 2 (0.1 µM, 110 to 222%), TX-A 2 (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 [ 3 H]thymidine incorporation. The results suggest that lyso-PC acts synergistically with the vasoactive compounds H 2 O 2 , TX-A 2 , 5-HT, Ang-II, ET-1, or U-II in inducing VSMC proliferation, which may play an important role in the progression of atherosclerosis. (Jpn Heart J 2002; 43: 409-416)
doi:10.1536/jhj.43.409 pmid:12227716 fatcat:ahut2qxdnzdmbit3fpqgujnx6m