title: Lysophosphatidic acid effects on atherosclerosis and thrombosis.
abstract: Lysophosphatidic acid (LPA) has been found to accumulate in high concentrations in atherosclerotic lesions. LPA is a bioactive phospholipid produced by activated platelets and formed during the oxidation of LDL. Accumulating evidence suggests that this lipid mediator may serve as an important risk factor for development of atherosclerosis and thrombosis. The role of LPA in atherogenesis is supported by the evidence that LPA: stimulates endothelial cells to produce adhesion molecules and chemoattractants; induces smooth muscle cells to produce inflammatory cytokines; stimulates smooth muscle cell dedifferentiation, proliferation, and migration; increases monocyte migration and decreases monocyte-derived cell emigration from the vessel wall; induces hypertension and vascular neointimal formation in vivo; and promotes plaque progression in a mouse atherosclerosis model. The role of LPA in thrombogenesis is supported by the evidence that LPA markedly induces the aggregation of platelets and the expression of tissue factor, which is the principal initiator of blood coagulation. Recent experimental data indicate that LPA is produced by specific enzymes and that LPA binds to and activates multiple G-protein-coupled receptors, leading to intracellular signaling. Therapeutics targeting LPA biosynthesis, metabolism and signaling pathways could be viable for prevention and treatment of atherosclerosis and thrombosis.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA.
authors.forename: Mei-Zhen
authors.initials: MZ
authors.lastname: Cui