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 platelets and having various effects on numerous cell types. We investigated some effects of 1-oleyl LPA on vascular smooth muscle cells cultured from adult human normal arteries. At micromolar concentrations, LPA induced a mitogenic effect ([3H]-thymidine incorporation and cell proliferation) on quiescent 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 mitogenactivated protein kinase. LPA inhibited cell migration through collagen coated membranes, with or without platelet-derived growth factor BB as chemoattractant. LPA induced a typical biphasic Ca2+ signal response made up of a rapid first 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.
Gennero
I
I
Service d'Hématologie, Fac. Pharmacie, Toulouse, France.
Xuereb
J M
JM
Simon
M F
MF
Girolami
J P
JP
Bascands
J L
JL
Chap
H
H
Boneu
B
B
Sié
P
P
D000328:Adult; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011460:Prostaglandins F / Q000494:pharmacology
D008246:Lysophospholipids; D011460:Prostaglandins F; D002118:Calcium