Coronary artery disease (CAD) is the leading cause of death and disability in the United States and other developed countries (1). CAD is characterized by the formation of atherosclerotic plaques in the walls of the coronary arteries (2–5). The structure of a normal coronary artery consists of the endothelium (a single layer of endothelial cells [ECs]) on the luminal side; followed by the intima, consisting of collagens and proteoglycans; the middle layer (media) of smooth muscle cells (SMCs); and the outside layer (adventitia), consisting of connective tissues, fibroblasts, and more SMCs (Figure 94.1). Development of CAD starts with binding of blood monocytes to the endothelium through cell adhesion molecules including vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1, followed by infiltration of lipoproteins and monocytes into the media region, which attract oxidized lipids and form foam cells, the hallmark of an arterial lesion. Necrosis and apoptosis of foam cells lead to a necrotic core with a mass of cell debris and lipids. Macrophages and the foam cells secrete cytokines, inflammatory molecules, and growth factors that induce SMC migration, proliferation, and the production of extra cellular matrix-forming plaques with fibrous caps. When the plaques are stable, the patient may not experience any symptoms of chest pain. However, plaque rupture may lead to thrombosis and secondary unstable angina, acute myocardial infarction (MI), or sudden death (6, 7).

This overview of the pathophysiology of CAD and MI represents the current prevailing mechanism for the pathogenesis of CAD and MI and suggests that CAD is an inflammatory process affecting the endothelium (i.e., endothelial dysfunction) in addition to a disease of lipid metabolism, SMC proliferation and migration, and up regulation of immune responses.