[Quantitative autoradiography].

The mechanism of the initiation and formation of the atherosclerotic plaque remains unclear. The response to injury hypothesis'-' suggests that endothelial cell loss induces intimal thickening and lipid accumulation, which are early steps in plaque formation. Many studies have confirmed that experimental de-endothelialization can induce an atherogenic response.l7&" A number of recent studies with experimental hypercholesterolemic animals,'"'' however, have observed more subtle morphological changes in the early stages of atherogenesis without the overt loss of endothelial cells. Apparent evidence of endothelial loss was not seen until plaque development was n ~ t a b l e . ' ~ ~ ' ~ Moreover, only a limited number of have demonstrated nonmechanically induced endothelial cell desquamation with exposure of the subendothelium. Furthermore, dead endothelial cells may remain a part of the intact monolayer until they are sloughed without exposing the underlying subendotheThe infrequency of naturally occurring de-endothelialization suggests that endothelial cell loss may not be a common cause for initiation of the atherogenic process. Instead of cell denudation, endothelial dysfunction without cell loss could be the first event in ather~genesis.~'