Fas Ligand-deficient Mice Display Enhanced Leukocyte Infiltration and Intima Hyperplasia in Flow-restricted Vessels

Abstract

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 α -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.