Inflammation, the endothelium, and the acute coronary syndromes.
Disruption of atherosclerotic plaques with associated thrombus is responsible for the majority of the acute coronary syndromes. Plaque instability is related closely to the degree of inflammation. Inflammatory cells within the plaque produce cytokines that inhibit collagen production by vascular smooth muscle cells and increase the production of metalloproteinases, which degrade the extracellular matrix in the fibrous cap. The recruitment of inflammatory cells into the vessel wall occurs in a coordinated sequence of events 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 the vessel wall. The cellular adhesion molecules are shed into the circulating blood in several disease states, including clinically evident atherosclerosis. The acute-phase reactants C-reactive protein and interleukin-6, and markers of the fibrinolytic state (plasminogen activator inhibitor-1 and tissue plasminogen activator), are also elevated in the acute coronary syndromes and in healthy individuals at increased risk for developing coronary artery disease. These markers may reflect vascular inflammation and thereby the stability of atherosclerotic plaques. Their measurement may pinpoint the mechanisms of benefit of cholesterol-lowering therapy and other interventions designed to reduce coronary risk, and potentially could offer a new method for monitoring coronary risk factor reduction in patients.
Kinlay
S
S
Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Selwyn
A P
AP
Libby
P
P
Ganz
P
P
D000208:Acute Disease; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D003327:Coronary Disease / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D013577:Syndrome
D015815:Cell Adhesion Molecules