Endothelial Cell Dysfunction and Injury in Experimental Hyperlipidemic Atherogenesis

Abstract

There is substantial evidence that the onset of atherosclerosis requires neither physical damage to endothelium nor platelet involvement.^{18,33,34,44,58,65–67} Endothelial denudation followed by platelet adhesion to the subendothelial structure appears to be a late event occurring in advance atherosclerotic lesions with marked tendency to thrombosis and subsequent lumen obstruction.^64,66 It is known that vascular endothelium participates in all major Physiopathologic processes involving the vessel wall, and that the earliest cellular event so far reported has been the focal adherence of monocytes to arterial endothelium. Bearing on this, we tried to identify and characterize the subtle biochemical and ultrastructural changes which appear in the lesion-prone areas of the artery wall, at the inception of atherogenesis before monocyte recruitment, during the so-called “prelesional” stage.^65,66 As experimental model, we chose the diet-induced hypercholesterolemia, a condition reputedly known to be alone capable of inducing both in humans and in experimental animals lipid accumulation in the intima leading to fatty streak formation that can evolve into a fibrous plaque.^{14,15,35,43,54,62,64,74}