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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/H2513    most recent 00865.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Damirin, A. Articles by Okajima, F. Search for Related Content PubMed PubMed Citation Articles by Damirin, A. Articles by Okajima, F.

Role of lipoprotein-associated lysophospholipids in migratory activity of coronary artery smooth muscle cells

¹Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan; ²Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Huhhot, Inner Mongolia, China; ³Research Laboratory, Kirin Brewery, Miyahara, Takasaki, Japan; and ⁴Laboratory of Pharmacology, College of Pharmacy, Pusan National University, Busan, Republic of Korea

Submitted 10 August 2006 ; accepted in final form 17 January 2007

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.

lysophosphatidic acid; sphingosine 1-phosphate; low-density lipoprotein; high-density lipoprotein; vascular smooth muscle cells

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				K. M. Argraves and W. S. Argraves HDL serves as a S1P signaling platform mediating a multitude of cardiovascular effects J. Lipid Res., November 1, 2007; 48(11): 2325 - 2333. [Abstract] [Full Text] [PDF]