Pathogenesis of atherosclerosis. Lipid infiltration of the artery wall originating from circulating LDL followed by oxidative modification in the subendothelial space, monocyte chemotaxis and foam cell formation are among the earliest events in atherogenesis. Monocytes differentiate into macrophages, followed by release of inflammatory mediators and a vicious cycle of inflammation. More advance stages of the disease include smooth muscle cell proliferation, formation of fibrous caps, necrotic cores, calcification, rupture, hemorrhage and thrombosis. Possible mechanisms how PM enhances atherosclerosis include: 1) Systemically translocated UFP or their chemical constituents may synergize with ox-PAPC generated within ox-LDL in the activation of proatherogenic molecular pathways in endothelial cells, 2) Inflammatory mediators released from the lungs may promote monocyte chemotaxis into the vessels, 3) PM can induce HDL dysfunction with loss of its antiinflammatory properties. Modified from Araujo and Lusis .