Anatomy of an atherosclerotic plaque. Hemodynamic forces at vulnerable points are predisposed to atherosclerotic lesions. It is at these vulnerable areas of the vasculature that fatty streaks, the earliest recognizable atherosclerotic lesions, form. These streaks are composed of macrophage which collect in the intima and are present in most individuals, including children. Fatty streaks are subclinical, but are the starting point for intermediate fibrofatty lesions. The intermediate fibrofatty lesion consists of several layers of lipid-engorged macrophage termed foam cells, which are intermixed with activated VSMCs which migrate from the media. Both cell types synthesize cytokines, which recruit more VSMCs from the media and immune cells from the circulation, maintaining a chronic, localized vascular inflammatory environment, leading to lesion growth. The fibrous plaque is an advanced lesion of greatest clinical importance and has an organized structure in which a necrotic core containing macrophage foam cells, dendritic cells, and T lymphocytes in various stages of apoptosis, as well as lipid deposits are covered by a dense cap of fibrous connective tissue consisting of activated smooth muscle cells, collagen, and other matrix components. Outward remodeling is a hallmark of this lesion, which helps maintain lumen diameter, but advanced plaques are the most clinically dangerous because of their vulnerability to rupture. Vulnerable plaques are those characterized by thin fibrous caps, and most thrombi result from fracture of this cap. The tendency of a plaque to rupture is associated with the structural integrity of its cap. The most clinically harmful consequences of the advanced plaque is its proclivity to cause thrombotic occlusions. Thin caps tend to correlate with high levels of IFNγ, which inhibits VSMC proliferation and collagen deposition in the cap, while simultaneously increasing synthesis of matrix degradation enzymes. Cellular constituents of an atherosclerotic lesion. The microenvironment of the atherosclerotic lesion is a dynamic gathering of resident vascular and infiltrating inflammatory cells. These cells include endothelial, vascular smooth muscle, T lymphocyte, monocyte, macrophage, macrophage foam cells, and dendritic cells. Cytokines produced by both resident vascular and infiltrating immune cells generate a complex milieu consisting of multiple cytokines which provides the driving mechanism for continued localized inflammation and progression of the atherosclerotic plaque.