Endothelial Activation: Its Role in Inflammation, Vascular Injury and Atherogenesis

Abstract

This chapter will briefly review evidence that endothelial cells respond to cytokines by undergoing a variety of functional and structural changes — collectively called endothelial activation — which may play a role in the pathogenesis of vascular injury, including atherogenesis, the major topic of this book. Endothelial injury is a component of most theories of atherogenesis, and is central to the “response to injury” hypothesis of atherosclerosis (Munro and Cotran 1988; Ross 1986). While the initial formulation of this theory presumed that denuding endothelial injury was an early and important event (Ross and Glomset 1976), it has since become clear that endothelial injury can be non-denuding, leading to so-called endothelial dysfunction (Gimbrone 1980). It has also become apparent that one of the earliest events in atherogenesis is the adhesion of leukocytes — principally monocytes — to the endothelium, followed by their emigration across the arterial wall, and transformation to foamy macrophages (reviewed by Gerrity in this volume). Because increased leukocyte adhesivity, as will presently be described, is one of the major manifestations of activated endothelium, its possible link to atherogenesis is obvious.