Effects of lysophosphatidic acid on proliferation and cytosolic Ca++ of human adult vascular smooth muscle cells in culture

Lysophosphatidic acid (LPA) is a lipid mediator generated by activated plat elets and having various effects on numerous cell types. We investigated so me effects of I-oleyl LPA on vascular smooth muscle cells cultured from adu lt human normal arteries. At micromolar concentrations, LPA induced a mitog enic effect ([H-3]-thymidine incorporation and cell proliferation) on quies cent cells, without an additional growth factor being required. This effect was equipotent to that of 10% fetal calf serum, and it was accompanied by early (5 minutes) and late (1-3 hours) phosphorylation of mitogen-activated protein kinase, LPA inhibited cell migration through collagen coated membr anes, with or without platelet-derived growth factor BE as chemoattractant. LPA induced a typical biphasic Ca2+ signal response made up of a rapid fir st phase due to Ca2+ release from intracellular stores followed by a second wave due to external Ca2+ influx. These findings support the proposal that LPA released from activated platelets is a mediator for smooth muscle cell response at the site of vessel injury in humans. (C) 1999 Elsevier Science Ltd. All rights reserved.