The role of inflammation in atherosclerosis.

The vascular endothelium serves as a dynamic interface between circulating blood elements and the interstitial tissues. As such, it communicates with cells in the vessel wall as well as with the surrounding tissue, sensing its environment and responding accordingly. The vasculature must maintain a delicate balance when initiating a functional response by producing both pro-inflammatory and anti-inflammatory mediators, vasoconstrictors and vasodilators, growth stimulators and inhibitors, and prothrombotic and anti-thrombogenic factors. Any response to injurious agents could lead to pathologic responses. One response to injury by the endothelium is the new or increased expression of surface receptors for immune elements. In atherosclerosis, the adhesion of monocytes and T cells to the endothelium is a key event triggered by some form of insult. Subsequent events include monocytic infiltration of the vessel wall, alterations in lipid metabolism, and the activation of these cells into foam cells. The presence of large numbers of foam cells in the intima may produce a high concentration of cytokines and growth factors within a localized area, extracellular matrix perturbations, smooth muscle cell proliferation, and ultimately platelet aggregation at the site of stenosis. Endothelial cells will propagate an inflammatory response long after the initial insult to the arterial vessel. Thus, all of the cellular elements of the vessel wall, as well as the atherosclerotic plaque itself, produce adhesive molecules, cytokines and growth factors that amplify and propagate the pathologic process.