Lysophosphatidylcholine Inhibits Endothelial Cell Migration and Proliferation via Inhibition of the Extracellular Signal–Regulated Kinase Pathway

作者: Yoshiyuki Rikitake , Seinosuke Kawashima , Tomoya Yamashita , Tomomi Ueyama , Satoshi Ishido

DOI: 10.1161/01.ATV.20.4.1006

关键词: Protein kinase AGrowth factorBasic fibroblast growth factorMAPK/ERK pathwayCell biologySignal transductionTyrosine phosphorylationFibroblast growth factorBiologyBiochemistryKinase

摘要: Abstract —Lysophosphatidylcholine (lysoPC), a major lipid component of oxidized low density lipoprotein, inhibits endothelial cell (EC) migration and proliferation, which are critical processes during angiogenesis the repair injured vessels. However, mechanism(s) lysoPC-induced inhibition EC proliferation has not been clarified. In this report, we demonstrate role extracellular signal–regulated kinase (ERK) in growth factor–stimulated as well their by lysoPC. stimulated basic fibroblast factor (FGF-2) were blocked ERK activity both specific mitogen-activated protein (MEK) 1 inhibitor PD98059 overexpression dominant-negative mutant MEK1. Conversely, constitutively active MEK1 increased comparable to those ECs with FGF-2. LysoPC inhibited FGF-2–induced activation via prevention Ras without inhibiting tyrosine phosphorylation phospholipase C-γ. Taken together, our data that is required for suggest Ras/ERK pathway lysoPC contributes reduced proliferation.

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