Cellular adhesion molecules and atherogenesis

Abstract

Atherosclerosis as manifested by coronary, cerebral, and peripheral arterial vascular disease is the leading cause of morbidity and mortality in the United States. Our understanding of the process of atherogenesis has evolved from the epidemiologic identification of cardiac risk factors to an increasing understanding of the molecular basis of vascular pathobiology. Evidence for the role of chronic inflammation in atherogenesis has been accumulating over the last decade and suggests that a generalized cellular and humoral inflammatory response promotes the formation of the atherosclerotic plaque. To target potential sites of intervention by which to inhibit or arrest the progression of atherosclerosis, an understanding of the molecular determinants of inflammation in the vasculature is critical. Localization of the cellular inflammatory response and regulation of the humoral inflammatory response are both mediated through the interactions of a group of specialized molecules, collectively referred to as cellular adhesion molecules. The cell-surface expression of these molecules in response to pathophysiological stimuli mediates the interaction between the endothelium and blood cells central to the development of atherosclerosis. As initially described, adhesion molecules serve as mediators of cell– cell and cell–matrix interactions. More recently, these molecules have been shown to participate in cell emigration, signaling functions, and other vascular physiological responses. The structure, function, and regulation of these specialized molecules in atherogenesis are the focus of this review.