High-density lipoprotein inhibits migration of vascular smooth muscle cells through its sphingosine 1-phosphate component.
High-density lipoprotein (HDL) is a well-established anti-risk factor against atherosclerosis, but the mechanism of its anti-atherogenic actions is not fully understood. Here, we examined the role of the HDL-associated sphingosine 1-phosphate (S1P), a lysolipid mediator, in the lipoprotein-induced actions in rat vascular smooth muscle cells (VSMCs). Both HDL and S1P inhibited platelet-derived growth factor-induced migration of VSMCs. The inhibitory effect was associated with an inhibition of cell spreading and these responses were reversed by a desensitization of VSMCs with S1P. HDL and S1P also inhibited migration of Chinese hamster ovary cells and this effect was enhanced by overexpressing S1P2 receptor. Finally, we showed that, even though S1P promoted DNA synthesis, HDL and S1P did not increase cell number of VSMCs. These findings suggest a novel mechanism for anti-atherogenic actions of HDL through its S1P component.
Tamama
Kenichi
K
Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.
Tomura
Hideaki
H
Sato
Koichi
K
Malchinkhuu
Enkhzol
E
Damirin
Alatangaole
A
Kimura
Takao
T
Kuwabara
Atsushi
A
Murakami
Masami
M
Okajima
Fumikazu
F
D000818:Animals; D016466:CHO Cells; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000096:biosynthesis; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000494:pharmacology*; D008246:Lysophospholipids / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D008075:Lipoproteins, HDL; D008246:Lysophospholipids; D010982:Platelet-Derived Growth Factor; C060506:sphingosine 1-phosphate; D004247:DNA; D013110:Sphingosine