Abstract
Lysophosphatidylcholine (LPC) is the major bioactive lipid component of oxidized LDL, thought to be responsible for many of the inflammatory effects of oxidized LDL described in both inflammatory and endothelial cells. Inflammation-induced transformation of vascular smooth muscle cells from a contractile phenotype to a proliferative/secretory phenotype is a hallmark of the vascular remodeling that is characteristic of atherogenesis; however, the role of LPC in this process has not been fully described. The present study tested the hypothesis that LPC is an inflammatory stimulus in coronary artery smooth muscle cells (CASMCs). In cultured human CASMCs, LPC stimulated time- and concentration-dependent release of arachidonic acid that was sensitive to phospholipase A2 and C inhibition. LPC stimulated the release of arachidonic acid metabolites leukotriene-B4 and 6-keto-prostaglandin F1α, within the same time course. LPC was also found to stimulate basic fibroblast growth factor release as well as stimulating the release of the cytokines GM-CSF, IL-6, and IL-8. Optimal stimulation of these signals was obtained via palmitic acid-substituted LPC species. Stimulation of arachidonic acid, inflammatory cytokines and growth factor release, implies that LPC might play a multifactorial role in the progression of atherosclerosis, by affecting inflammatory processes.
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Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogeneicity. New Engl J Med 320: 915–924
Parthasarathy S, Steinbrecher UP, Barnett J, Witztum JL, Steinberg D. (1985) Essential role of phospholipase A2 activity in endothelial cell-induced modification of low density lipoprotein. Proc Natl Acad Sci USA 82: 3000–3004
Young IS, McEneny J (2001) Lipoprotein oxidation atherosclerosis. Biochem Soc Trans 29(Pt 2): 358–362
Prokazova NV, Zvezdina ND, Korotaeva AA. (1995) Effect of lysophosphatidylcholine on transmembrane signal transduction. Biochemistry (Mosc) 63: 31–37
Chen Y, Jiang B, Chen S, Yasuda O, Hirotani A, Ogihara T. (1995) Lysophosphatidylcholine causes Ca2+ influx, enhanced DNA synthesis and cytotoxicity in cultured vascular smooth muscle cells. Atherosclerosis 112: 69–76
Chai Y-C, Howe PH, Di Corleto PE, Chisolm GM. (1996) Oxidized low density lipoprotein and lysophosphatidyl choline stimulate cell cycle entry in vascular smooth muscle cells. J Biol Chem 271: 17791–17797
Stiko A, Regnstrom J, Shah PK, Cercek B, Nilsson J. (1996) Active oxygen species and lysophosphatidylcholine are involved in oxidized low density lipoprotein activation of smooth muscle cell DNA synthesis. Arterioscler Thromb Vasc Biol 16:194–200
Kume N, Cybulsky MI, Gimborne MJ. (1992) Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest 90:1138–1144
Kume N, Gimborne MJ. (1994) Lysophosphatidylcholine transcriptionally induces growth factor gene expression in cultured human endothelial cells. J Clin Invest 93: 907–911
Takahara N, Kashiwagi A, Maegawa H, Shigeta Y. (1996) Lysophosphatidylcholine stimulates the expression and production of MCP-1 by human vascular endothelial cells. Metabolism 45: 559–564
Wong JT, Tran K, Pierce GN, Chan AC, Karmin O, Choy PC (1998) Lysophosphatidylcholine stimulates the release of arachidonic acid in human endothelial cells. J Biol Chem 273: 6830–6836
Kugiyama K, Sugiyama S, Ogata N, Oka H, Doi H, Ota Y, Yasue H. (1999) Burst production of superoxide anion in human endothelial cells by lysophosphatidylcholine. Atherosclerosis 143: 201–204
Chisolm GM3rd, Chai Y. (2000) Regulation of cell growth by oxidized LDL. Free Radic Biol Med 28: 1697–1707
Dickson BC, Gotlieb AI. (2003) Towards understanding acute destabilization of vulnerable atherosclerotic plaques. Cardiovasc Path 12: 237–248
Rong JX, Berman JW, Taubman MB, Fisher EA. (2002) Lysophosphatidylcholine stimulates monocyte chemoattractant protein-1 gene expression in rat aortic smooth muscle cells. Arterioscler Thromb Vasc Biol 22(10): 1617–1623
Palinski W, Rosenfeld ME, Yla-Herttuala S, Gurtner GC, Socher SS, Butler SW, Parthasarathy S, Carew TE, Steinberg D, Witztum JL. (1989) Low density lipoprotein undergoes oxidative modification in vivo. Proc Natl Acad Sci U S A 86: 1372–1376
Golfman LS, Haughey NJ, Wong JT, Jiang JY, Lee D, Geiger JD, Choy PC (1999) Lysophosphatidylcholine induces arachidonic acid release and calcium overload in cardiac myoblastic H9c2 cells J Lipid Res 40: 1818–1826
Abdel-Latif AA. (1995) Phosphoinositides and arachidonic acid signaling systems in the mammalian iris. Prog Retin Eye Res 14: 75–107
Natarajan R, Nadler JL. (2004) Lipid inflammatory mediators in diabetic vascular disease. Arterioscler Thromb Vasc Biol 24: 1542–1548
Leslie CC. (2004) Regulation of arachidonic acid availability for eicosanoid production. Biochem Cell Biol 82: 1–17
Mehrabian M, Allayee H. (2003) 5-lipoxygenase and atherosclerosis. Curr Opin Lipidol 14: 447–457
Aiello RJ, Bourassa PA, Lindsey S, Weng W, Freeman A, Showell HJ. (2002) Leukotriene B4 receptor antagonists reduces monocytic foam cells in mice. Arterioscler Thromb Vasc Biol 22: 443–449
Subbarao K, Jala VR, Mathis S, Suttles J, Zacharias W, Ahamed J, Ali H, Tseng MT, Haribabu B. (2004) Role of leukotriene B4 receptors in the development of atherosclerosis: Potential Mechanisms. Arterioscler Thromb Vasc Biol 24: 369–375
Zembowicz A, Jones SL, Wu KK. (1995) Induction of cyclooxygensase-2 in human umbilical cells by lysophosphatidylcholine. J Clin Invest 96: 1688–1692
Rikitake Y, Hirata K, Kawashima S, Takeuchi S, Shimokawa Y, Kojima Y, Inoue N, Yokoyama M. (2001) Signaling Mechanism underlying COX-2 induction by lysophosphatidylcholine. Biochem Biophys Res Comm 281: 1291–1297
Vane JR, Bakhle YS, Botting RM (1998) Cyclooxygenases 1 and 2 Annu Rev Pharmacol Toxicol 38: 97–120
Linton MF, Fazio S. (2004) Cyclooxygenase-2 and inflammation in atherosclerosis. Curr Opin Pharmacol 4: 116–123
Nishi E, Kume N, Ueno Y, Ochi H, Moriwaki H, Kita T. (1998) Lysophosphatidylcholine enhances cytokine-induced interferon gamma expression in human T lymphocytes. Cir Res 83: 508–515
Liu-Wu Y, Hurt-Camejo E, Wiklund O. (1998) Lysophosphatidylcholine induces the production of IL-1beta by human monocytes. Atherosclerosis 137: 351–357
Spangelo BL, Jarvis D (1996) Lysophosphatidylcholine stimulates interleukin-6 release from rat anterior pituitary cells in vitro Endocrinology 137: 4419–4426
Takahara N, Kashiwagi A, Maegawa H, Shigeta Y (1996) Lysophosphatidylcholine stimulates the expression and production of MCP-1 by human vascular endothelial cells. Metabolism 45: 559–564
Rong JX, Berman JW, Taubman MB, Fisher EA (2002) Lysophosphatidylcholine stimulates monocyte chemoattractant protein-1 gene expression in rat aortic smooth muscle cells. Arterioscler Thromb Vas Biol 22: 1617–1623
Rus HG,Vlaicu R, Niculescu F (1996) Interleukin-6 and interleukin-8 protein and gene expression in human arterial atherosclerotic wall. Atherosclerosis 127(2): 263–271
Libby P, Ross R (1996) Cytokines and growth regulatory molecules In: Fuster V, Ross R, Topol EJ (eds), Atherosclerosis and coronary artery disease Vol 1. Philadelphia Lippincott-Raven 585–594
Zhao L, Funk CD. (2004) Lipoxygenase pathways in atherogenesis. Trends Cardiovasc Med 14: 191–195
Yeh ET. (2004) CRP as a Mediator of Disease, Circulation 109: 11–14
Ikeda U, Ikeda M, Oohara T, Oguchi T, Kamitani Y, Kane S. (1991) Interleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner. Am J Physiol Heart Circ Physiol 260: H1713-H1717
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We thank Carol D. Manning for cytokine measurement.
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Aiyar, N., Disa, J., Ao, Z. et al. Lysophosphatidylcholine induces inflammatory activation of human coronary artery smooth muscle cells. Mol Cell Biochem 295, 113–120 (2007). https://doi.org/10.1007/s11010-006-9280-x
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DOI: https://doi.org/10.1007/s11010-006-9280-x