Expression of VCAM-1 in rabbit iliac arteries is associated with vasodilator dysfunction of regenerated endothelium following balloon injury

Abstract

Previous studies have demonstrated impaired endothelium-dependent vasodilation following balloon injury of the rabbit iliac artery, suggesting dysfunction of the regenerated endothelium. More recently, expression of vascular cell adhesion molecule-1 (VCAM-1) has been shown up to 4 weeks in a different injury model of the rabbit aorta, suggesting sustained inflammatory activation of endothelium following injury. The aim of the present study was to combine the examination of VCAM-1 expression, as a marker of cellular activation, and the assessment of endothelium-dependent relaxation to test the hypothesis that different forms of altered endothelial function are concurrently present in the chronic phase following experimental balloon angioplasty. New Zealand White rabbits fed either a standard ( n = 7) or a 1% cholesterol ( n = 8) diet, underwent balloon injury of the iliac artery 5 weeks following the initiation of the diet. Four weeks after balloon injury, control and balloon-injured arteries were harvested for in vitro studies of vascular reactivity, for morphometric analysis and for immunocytochemical staining with Rb 1 9 monoclonal antibody directed against VCAM-1 and with CD 31 monoclonal antibody for the identification of endothelial cells. The combination of balloon injury and hypercholesterolemia resulted in a marked impairment of endothelium-dependent relaxation to acetylcholine and in a pronounced intimal proliferation compared to control or either intervention alone. Control rings of rabbits fed a normal diet did not reveal positive staining for VCAM-1. Balloon-injured rings of the animals fed a normal diet showed focal areas of positive staining in the superficial cell layer overlying intimal lesions. In the group fed a high cholesterol diet, control rings and ballooned rings showed positive staining for VCAM-1 in cells overlying intimal lesions. In all groups the superficial cell layers were identified as endothelial cells by positive staining for CD 31. In conclusion, the present study shows that regenerated endothelium following mechanical arterial injury reveals expression of VCAM-1 together with impaired receptor-mediated vasodilator capacity. Thus, the expression of VCAM-1 and the impairment of endothelium-dependent relaxation may represent different features of endothelial dysfunction following balloon injury which may actively influence the proliferative lesion of restenosis after balloon angioplasty.