Effects of Lysophosphatidic Acid on Proliferation and Cytosolic Ca ++ of Human Adult Vascular Smooth Muscle Cells in Culture

• Published in: Thrombosis research Vol. 94; no. 5; pp. 317 - 326
• Main Authors: Gennero, Isabelle, Xuereb, Jean-Marie, Simon, Marie-Françoise, Girolami, Jean-Pierre, Bascands, Jean-Louis, Chap, Hugues, Boneu, Bernard, Sié, Pierre
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 01.06.1999; Elsevier Science
• Subjects: Adult; Atherosclerosis; Biological and medical sciences; Blood Platelets - metabolism; Blood vessels and receptors; Calcium - metabolism; Cell Communication; Cell Division - drug effects; Cell Movement - drug effects; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Humans; Intracellular calcium; Lysophosphatidic acid; Lysophospholipids - pharmacology; Mitogenic effect; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Prostaglandins F - pharmacology; Smooth muscle cells; Vertebrates: cardiovascular system; PBS, phosphate-buffered-saline; Lysophosphatidic acid; Intracellular calcium; MAPK, mitogen-activated protein kinases; Atherosclerosis; Mitogenic effect; Smooth muscle cells; LPA, lysophosphatidic acid; PDGF, platelet-derived growth factor; VSMC, vascular smooth muscle cells; FCS, fetal calf serum; Human; Cell culture; Calcium; Blood vessel; Adult; Smooth muscle; Circulatory system; Biological effect; Cytosol
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/S0049-3848(99)00004-3

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 mitogen-activated 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 Ca 2+ signal response made up of a rapid first phase due to Ca 2+ release from intracellular stores followed by a second wave due to external Ca 2+ 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.