Inflammation, the endothelium, and the acute coronary syndromes

Disruption of atherosclerotic plaques with associated thrombus is responsib le for the majority of the acute coronary syndromes. Plaque instability is related closely to the degree of inflammation. Inflammatory cells within th e plaque produce cytokines that inhibit collagen production by vascular smo oth muscle cells and increase the production of metalloproteinases, which d egrade the extracellular matrix in the fibrous cap. The recruitment of infl ammatory cells into the vessel wall occurs in a coordinated sequence of eve nts involving the expression of cellular adhesion molecules on the surface of activated endothelial cells and the production of chemoattractants, and occurs in part in response to oxidation of low-density lipoprotein within t he vessel wall. The cellular adhesion molecules are shed into the circulati ng blood in several disease states, including clinically evident atheroscle rosis. The acute-phase reactants C-reactive protein and interleukin-6, and markers of the fibrinolytic state (plasminogen activator inhibitor-1 and ti ssue plasminogen activator), are also elevated in the acute coronary syndro mes and in healthy individuals at increased risk for developing coronary ar tery disease. These marker?; may reflect vascular inflammation and thereby the stability of atherosclerotic plaques. Their measurement may pinpoint th e mechanisms of benefit of cholesterol-lowering therapy and other intervent ions designed to reduce coronary risk, and potentially could offer a new me thod for monitoring coronary risk factor reduction in patients.