出版社：American Society for Biochemistry and Molecular Biology
摘要：Previous studies have shown apolipoprotein E (apoE) recruitmentto medial layers of carotid arteries after vascular injury invivo and apoE activation of inducible nitric oxide synthase(iNOS) in smooth muscle cells in vitro. This investigation exploredthe relationship between medial apoE recruitment and iNOS activationin protection against neointimal hyperplasia. ApoE was presentin both neointimal-resistant C57BL/6 mice and neointimal-susceptibleFVB/N mice 24 h after carotid denudation, but iNOS expressionwas observed only in the neointimal-resistant C57BL/6 mice.However, iNOS was not observed in apoE-defective C57BL/6 mice.In contrast, overexpression of apoE in FVB/N mice activatediNOS expression in the injured vessels, resulting in protectionagainst neointimal hyperplasia. ApoE and iNOS were colocalizedin the medial layer of neointimal-resistant mouse strains. Endothelialdenudation of carotid arteries in the iNOS-deficient NOS2–/–mice did not increase neointimal hyperplasia but significantlyincreased medial thickness and area. The iNOS-specific inhibitoralso abrogated the apoE protective effects on vascular responseto injury in apoE-overexpressing FVB/N mice.
Thus, injury-induced activation of iNOS requires apoE recruitment.Moreover, both apoE and iNOS are necessary for the suppressionof cell proliferation, and apoE recruitment without iNOS expressionresulted in medial hyperplasia without cell migration to theintima.Abbreviations: apoE, apolipoprotein E; COX-2, cyclooxygenase-2; iNOS, inducible nitric oxide synthase; LRP-1, low density lipoprotein receptor-related protein-1
Supplementary key words neointimal hyperplasia • smooth muscle cells • endothelial denudation • vascular biology • transgenic mice
