Figure 3. Infection-induced stimulation of accelerated atherosclerosis by immunological sounding. Persistent local infection, such as oral infections by P. gingivalis, may promote atherosclerosis via chronic up-regulation of inflammatory cascades involving TNF-, IL-1, IFN, IL-8, MCP-1, and CRP. These cytokines, chemokines, and acute phase mediators could be shed into the vasculature from a focus of P. gingivalis infection in the periodontium. Once in the circulation, these mediators may subsequently activate vascular endothelial cells in a manner that shifts them from a normally anti-thrombotic state to one expressing high levels of inflammatory mediators, including CAMs (blue triangles) and TLRs (green trapezoid), that become pro-thrombotic. This activated endothelium would likely be a site for subsequent atheroma formation, independent of direct pathogen involvement at this site. This further immunological activation results in the recruitment of monocytes, as well as the stimulation, migration, and proliferation of smooth-muscle cells that, together with elevated levels of circulating lipids such as ox-LDL, ultimately results in acceleration of the atheroma.