Smooth muscle LDL receptor-related protein-1 inactivation reduces vascular reactivity and promotes injury-induced neointima formation.

Objective: Defective smooth muscle expression of LDL receptor-related protein-1 (Lrp1) increases atherosclerosis in hypercholesterolemic mice. This study explored the importance of smooth muscle Lrp1 expression under normolipidemic conditions.

Methods And Results: Smooth muscle cells isolated from control (smLrp1(+/+)) and smooth muscle-specific Lrp1 knockout (smLrp1(-/-)) mice were characterized based on morphology, smooth muscle marker protein expression levels, and growth rates in vitro.

Apolipoprotein E inhibition of vascular hyperplasia and neointima formation requires inducible nitric oxide synthase.

Previous studies have shown apolipoprotein E (apoE) recruitment to medial layers of carotid arteries after vascular injury in vivo and apoE activation of inducible nitric oxide synthase (iNOS) in smooth muscle cells in vitro. This investigation explored the relationship between medial apoE recruitment and iNOS activation in protection against neointimal hyperplasia. ApoE was present in both neointimal-resistant C57BL/6 mice and neointimal-susceptible FVB/N mice 24 h after carotid denudation, but iNOS expression was observed only in the neointimal-resistant C57BL/6 mice.

Vascular apolipoprotein e expression and recruitment from circulation to modulate smooth muscle cell response to endothelial denudation.

Apolipoprotein E (apoE) has been shown previously to have anti-proliferative and anti-migratory effects on smooth muscle cells in culture. In addition, overexpression of the apoE gene also reduces neointimal hyperplasia in mice after endothelial denudation. In this investigation, immunohistochemical techniques were used to demonstrate that apoE was present in the medial smooth muscle layers of the carotid artery between 1 and 28 days after endothelial cell denudation.