摘要：

Lysophosphatidylcholine (LPC) is a major bioactive phospholipid component of oxidized low-density lipoprotein (Ox-LDL) and is implicated as a critical factor in the atherogenic activity of Ox-LDL. LPC is believed to play an important role in atherosclerosis and inflammatory diseases by altering various functions in a number of cell-types. We have examined that LPC stimulated the proliferation and migratory responses of cultured human vascular smooth muscle cells(VSMC),and these actions were inhibited by Ki16425,a receptor antagonist for the ATX enzymatic product lysophosphatidic acid (LPA) . We also find that ATX were strongly expressed in the cells. However, the ATX product mediating the increase in cellular proliferation and motility remain to be identified. Here,we reported that ATX expressed in the cells contributes to Lpc-induced VSMC Proliferation and migration .Results: LPC and LPA stimulated hVSMCs proliferation and migration in a PTX-sensitive manner. These actions were suppressed by using SiRNA sepecific to ATX and LPA1 receptor,Ki16425. Furthermore, The LPC- and LPA-induced proliferation of hVSMCs was markedly inhibited by a potent calcineurin inhibitor cyclosporine A and PD98059,a ERK inhibitor. Instead, an epidermal growth factor (EGF) receptor tyrosine kinase inhibitor and P38 inhibitor markedly suppressed the migration response to LPC and LPA without having any significant effect on proliferation of VSMC. .Conclusion: The LPC-induced stimulation of proliferation in VSMC is mediated by the ATX enzymatic product LPA through LPA1receptors / Gi/o-proteins/ ERK- MAP kinase /Ca2+/calcineurin pathways . The migration response to LPC and LPA are mediated by the ATX enzymatic product LPA through LPA1-receptors / Gi/o-proteins/ P38- MAP kinase signaling pathway and also mediated by transactivation of EGF receptor pathways .

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