Fas ligand-deficient mice display enhanced leukocyte infiltration and intima hyperplasia in flow-restricted vessels.
Fas ligand (FasL) is a death factor that induces apoptosis in Fas-bearing cells. To explore the role of FasL in vascular lesion formation, we analysed leukocyte infiltration and lesion formation in a flow-restriction model of vascular injury that results in neointima formation in the presence of intact endothelium. The left common carotid arteries of wild-type and FasL-deficient (gld) mice were ligated just proximal to the carotid bifurcation. Three days after the ligation, T lymphocyte and macrophage infiltration into the common carotid artery was notably enhanced in the gld mice relative to the wild-type C57BL/6J mice. Four weeks after the ligation, the common carotid arteries developed neointima-like lesions consisting primarily of alpha -smooth muscle actin-positive cells beneath an endothelial cell monolayer. Neointima formation was greater in the gld mice than in wild-type mice. These data provide mouse genetic evidence suggesting that Fas-mediated cell death can function to restrict inflammation and intimal hyperplasia during vascular remodelling.
Sata
M
M
Division of Cardiovascular Research, Tufts University School of Medicine, Boston, MA 02135, USA.
Walsh
K
K
D000199:Actins / Q000378:metabolism; D000818:Animals; D053222:Fas Ligand Protein; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017354:Point Mutation; D013997:Time Factors; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*
D000199:Actins; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins