The Effect Of LPC On VSMCs Proliferation And Its Signaling Pathway

AIM:To study the effect of lysophosphatidylcholine (LPC) on proliferation of vascular smooth muscle cells (VSMCs) and it's signaling pathway involved in the proliferation.Content:VSMCs were cultured and stimulated by LPA, and LPC at present with or without Ki16425 (An antagonist of LPA1 receptor) and PTX for 2 to 3 days, then their proliferation was measured by MTT assay. Gene expression of lysophospholipid receptors and autotaxin were determined by real-time quantitative PCR. Western blot assay was used to detect the ERK1/2 phosphorylation levels before and after the stimulation with LPA, at present with or without Ki 16425 and PTX.Results:MTT assay showed that both the LPA and LPC stimulated VSMCs proliferation, which could be inhibited by Ki16425 or PTX. Real time quantitative PCR analysis showed that all five receptors of LPA are expressed in AoSMCs, among which the expression of LPA1 is far higher than others. The gene that encoding autotaxin is highly expressed in AoSMCs, and autotaxin has phospholipase D activity that hydrolyze LPC to LPA. Western blot analysis showed that LPA, LPC and PDGF can stimulate ERK phosphorylation all alone. Both the Ki 16425 and PTX decrease the expression of P-ERKI/2 induced by LPA and LPC, but not by PDGF.Conclusion:1) In this study, we found that autotaxin expressed in the cells was related to the cell proliferation induced by LPC. And autotaxin have high phospholipase D activity.2) LPC can stimulate LPA1 receptor through both the LPC-LPA1 and LPC-LPA-LPA1 pathway, and induce cell proliferation through LPA1-Gi-ERK pathway in VSMCs.3) ox-LDL and its content LPC are important factors for induced atherosclerosis. Thus controlling the concentration of ox-LDL in blood is important in preventing and curing the atherosclerosis.