Regular articleEffects of Lysophosphatidic Acid on Proliferation and Cytosolic Ca++ of Human Adult Vascular Smooth Muscle Cells in Culture☆
Section snippets
Materials
1-oleoyl-sn-glycero-3-phosphate (18:1 LPA), fatty acid–free bovine serum albumin (BSA), thapsigargin and neomycin were from Sigma Chemical Co. (St. Louis, MO, USA). Fetal calf serum (FCS), Dulbecco’s Modified Eagle’s Medium (DMEM), and trypsin were from Seromed (Berlin, Germany). [3H]-thymidine was from New Life Sciences Products (Boston, MA, USA), fura-2 AM from Molecular Probes Inc. (Eugene, OR, USA). Plastic material for culture and inserts for migration experiments were from Nunclon Inter
Results
LPA induces a dose-dependent mitogenic effect on VSMCs. Figure 1 shows the effects of LPA on [3H]-thymidine incorporation in serum-starved VSMCs. The increase was statistically significant at the lowest LPA concentration used (1 μM) and maximal at 5 μM (2.5-fold the value obtained in the absence of LPA and 80% of that obtained with 10% FCS). Figure 2 shows the effect of LPA on cell proliferation. Seventy-two hours after the addition of LPA, the cell number increased dose-dependently. The
Discussion
Relatively few studies have been devoted to the effects of LPA on smooth muscle cells of vascular origin 16, 17, 18, 19. The present study is the first report of LPA action on VSCMs from normal human arteries. At micromolar concentrations, LPA appears to be equipotent to 10% FCS in inducing DNA synthesis and cell division. Optimal LPA concentrations reported in this study are different from those found by others 17, 18. This may be due in part to the use of different animal species. Tokumura et
Acknowledgements
The authors thank Dr. G. Fournial and Y. Glock (Department of Vascular Surgery) for providing human mammary arteries.
References (30)
Lysophosphatidic acid, a multifunctional phospholipid messenger
J Biol Chem
(1995)LPAA novel lipid mediator with diverse biological actions
Trends Cell Biol
(1994)- et al.
Lysophosphatidic acidG-protein signalling and cellular responses
Curr Opin Cell Biol
(1997) - et al.
Lysophophatidic acid as a phospholipid mediatorPathways of synthesis
FEBS Lett
(1997) - et al.
Phosphatidic and lysophosphatidic acid production in phospholipase C and thrombin-treated platelets. Possible involvment of a platelet lipase
Biochimie
(1978) - et al.
Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells
Cell
(1995) - et al.
Molecular cloning of the human Edg2 protein and its identification as a functional cellular receptor for lysophosphatidic acid
Biochim Biophys Res Comm
(1997) - et al.
Identification of the molecular species of lysophosphatidic acid produced when platelets are stimulated by thrombin
Biochim Biophys Acta
(1989) - et al.
Dual effect of lysophosphatidic acid on proliferation of glomerular mesangial cells
Kidney Int
(1997) - et al.
Lysophosphatidic acid and intracellular signalling in vascular smooth muscle cells
Atherosclerosis
(1997)
Oxidized low density lipoprotein-mediated activation of phospholipase D in smooth muscle cellsA possible role in cell proliferation and atherogenesis
J Lipid Res
Coordinate, biphasic activation of 44 mitogen-activated protein kinase and 56 kinase by growth factors in hamster fibroblasts
J Biol Chem
Lysophosphatidate-induced cell proliferationIdentification and dissection of signalling pathways mediated by G proteins
Cell
Lysophosphatidic acid stimulates mitogen-activated protein kinase activation via a G-protein-coupled pathway requiring p21ras and p74raf-1
J Biol Chem
Lysophosphatidic acid, but not phosphatidic acid, is a potent Ca2+ mobilizing stimulus for fibroblasts
J Biol Chem
Cited by (42)
Atherosclerotic lesion progression changes lysophosphatidic acid homeostasis to favor its accumulation
2010, American Journal of PathologyRoles of lysophosphatidic acid in cardiovascular physiology and disease
2008, Biochimica et Biophysica Acta - Molecular and Cell Biology of LipidsBiology of LPA in health and disease
2004, Seminars in Cell and Developmental BiologyMolecular mechanisms of lysophosphatidic acid action
2003, Progress in Lipid ResearchEpicardial and Pericoronary Adipose Tissue, Coronary Inflammation, and Acute Coronary Syndromes
2023, Journal of Clinical Medicine
- ☆
Presented in part at the XVIth Congress of the International Society for Thrombosis and Haemostasis, Florence, Italy, 6–12 June, 1997.