and by CD40/CD40 ligand (CD40L and CD154) interactions. 18–22 Once adherent, the monocytes transmigrate into the tunica intima, the innermost layer of the arterial wall, passing between the ECs. This monocyte migration is directed along a concentration gradient of MCP-1, via interaction with the monocyte receptor CCR2. 23 Once within the arterial intima, the monocytes develop into macrophages and begin to express scavenger receptors, such as SR-A, CD36, and LOX-1, that internalize modified lipoproteins. 24, 25 Internalization of these lipoprotein particles gives rise to lipidladen macrophages or foam cells, which characterize early atherosclerotic lesions. Within the developing atheroma, the foam cells begin to secrete proinflammatory cytokines that maintain a chemotactic stimulus for adherent leukocytes, augment expression of scavenger receptors, and promote macrophage replication. 6

However, macrophages are not alone in contributing to atheroma formation. T cells, dendritic cells, and mast cells are also recruited into atheromatous plaques. 26 Binding to adhesion molecules, such as VCAM-1, facilitates T-cell entry into the intima. Once within the arterial intima, T cells may become activated by encountering antigens such as ox-LDL and begin to secrete cytokines that can influence macrophage activity. CD40/CD40L engagement between activated T cells and macrophages can result in the expression of tissue factor (TF), matrix metalloproteinases (MMPs), and proinflammatory cytokines that perpetuate the inflammatory response. 6 Plaque formation is further promoted by the less abundant mast cells. On mast cell degranulation, TNF-, heparin, and serine proteases are released. 6 If the risk factors inducing endothelial dysfunction and inflammation remain, the atheroma will progress from a fatty streak to a more complex lesion.