Regulation of arterial lesions in mice depends on differential smooth muscle cell migration: a role for sphingosine-1-phosphate receptors.
The response of mice arteries to injury varies significantly between strains. FVB mice develop large neointimas after injury, whereas very small lesions form in C57BL/6 mice. After injury, platelet interaction with the denuded artery and early smooth muscle (SMC) replication are identical in both strains; however, the migration of SMCs differs significantly. FVB cells readily move into the developing neointima, whereas only the occasional C57BL/6 cells migrate. Injured arteries showed no difference in matrix metalloproteinases (MMP-2 and MMP-9) and plasminogen activator activities. In vitro, sphingosine-1-phosphate (S1P) in combination with platelet-derived growth factor (PDGF) stimulates migration of FVB cells but inhibits migration of C57BL/6 SMCs. Both SMCs migrate equally well to PDGF alone. One explanation is that the SMCs express different S1P receptors. Real-time polymerase chain reaction shows that FVB cells express higher levels of S1P receptor-1 (S1P(1)) compared with C57BL/6 cells, which express higher levels of S1P receptor-2 (S1P(2)). In addition, the migration of C57BL/6 cells can be increased by inhibiting S1P(2), whereas inhibiting S1P(1) expression slows the migration of FVB cells. Taken together these studies suggest that expression of S1P receptors vary within inbred mouse strains and that S1P is critical for SMC migration and lesion formation after injury.
Inoue
Shinya
S
Department of Pathology, University of Washington, Seattle, WA 98108, USA.
Nakazawa
Tatsu
T
Cho
Aesim
A
Dastvan
Frank
F
Davastan
Frank
F
Shilling
Dustin
D
Daum
Günter
G
Reidy
Michael
M
D000818:Animals; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010960:Plasminogen Activators / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D049349:Receptors, Lysosphingolipid; D010960:Plasminogen Activators; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9