Role of lipoprotein-associated lysophospholipids in migratory activity of coronary artery smooth muscle cells
- 1 May 2007
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 292 (5), H2513-H2522
- https://doi.org/10.1152/ajpheart.00865.2006
Abstract
The migration of vascular smooth muscle cells (SMCs) is a hallmark of the pathogenesis of atherosclerosis and restenosis after angioplasty. Plasma low-density lipoprotein (LDL), but not high-density lipoprotein (HDL), induced the migration of human coronary artery SMCs (CASMCs). Among bioactive lipids postulated to be present in LDL, lysophosphatidic acid (LPA) appreciably mimicked the LDL action. In fact, the LDL-induced migration was markedly inhibited by pertussis toxin, an LPA receptor antagonist Ki-16425, and a small interfering RNA (siRNA) targeted for LPA1 receptors. Moreover, LDL contains a higher amount of LPA than HDL does. HDL markedly inhibited LPA- and platelet-derived growth factor (PDGF)-induced migration, and sphingosine 1-phosphate (S1P), the content of which is about fourfold higher in HDL than in LDL, mimicked the HDL action. The inhibitory actions of HDL and S1P were suppressed by S1P2 receptor-specific siRNA. On the other hand, the degradation of the LPA component of LDL by monoglyceride lipase or the antagonism of LPA receptors by Ki-16425 allowed LDL to inhibit the PDGF-induced migration. The inhibitory effect of LDL was again suppressed by S1P2 receptor-specific siRNA. In conclusion, LPA/LPA1 receptors and S1P/S1P2 receptors mediate the stimulatory and inhibitory migration response to LDL and HDL, respectively. The balance of not only the content of LPA and S1P in lipoproteins but also the signaling activity between LPA1 and S1P2 receptors in the cells may be critical in determining whether the lipoprotein is a positive or negative regulator of CASMC migration.Keywords
This publication has 53 references indexed in Scilit:
- Rho and vascular diseaseAtherosclerosis, 2005
- Role of p38 mitogen-activated kinase and c-Jun terminal kinase in migration response to lysophosphatidic acid and sphingosine-1-phosphate in glioma cellsOncogene, 2005
- The G Protein–Coupled Receptor S1P2 Regulates Rho/Rho Kinase Pathway to Inhibit Tumor Cell MigrationCancer Research, 2005
- Sphingosine 1-Phosphate Receptors Mediate the Lipid-Induced cAMP Accumulation through Cyclooxygenase-2/Prostaglandin I2Pathway in Human Coronary Artery Smooth Muscle CellsMolecular Pharmacology, 2004
- The ins and outs of lysophosphatidic acid signalingBioEssays, 2004
- Circulating lipoproteins as proinflammatory and anti-inflammatory particles in atherogenesisCurrent Opinion in Lipidology, 2003
- Ligand-dependent Inhibition of B16 Melanoma Cell Migration and Invasion via Endogenous S1P2 G Protein-coupled ReceptorPublished by Elsevier BV ,2003
- Oxidatively modified LDL contains phospholipids with platelet-activating factor-like activity and stimulates the growth of smooth muscle cells.JCI Insight, 1995
- Sphingosine-1-phosphate inhibits PDGF-induced chemotaxis of human arterial smooth muscle cells: spatial and temporal modulation of PDGF chemotactic signal transduction.The Journal of cell biology, 1995
- Oxidized low‐density lipoprotein is chemotactic for arterial smooth muscle cells in cultureFEBS Letters, 1990