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Figure 2. Direct invasion of vascular endothelium. (A) In this model, invasion of the vascular endothelium by pathogenic bacteria such as P. gingivalis (red circles) results in the induction of a local inflammatory response, defined by the expression of cell adhesion molecules (CAMs; green trapezoid), Toll-like receptor (TLRs; blue triangle), chemokines, and cytokines. These inflammatory molecules have all demonstrated significant roles in the initiation and/or acceleration of atherosclerosis. The ability of P. gingivalis to stimulate host endothelial cell activation, both in vitro and in vivo, is a function of surface-expressed major fimbriae. P. gingivalis that does not possess fimbriae (fimA) fails to enter endothelial cells efficiently, whereas those organisms that possess fimbriae (wild-type, WT) readily enter these cells (Deshpande et al., 1998b; Khlgatian et al., 2002; Nassar et al., 2002). Following uptake, P. gingivalis-infected endothelial cells, possibly via a receptor-mediated signaling event, activate gene transcription and stimulate these cells to produce a variety of innate immune markers, including CAMs (ICAM-1, VCAM-1), TLRs (TLR-2, TLR-4), pro-inflammatory cytokines (TNF-
, IL-1ß), and chemokines (MCP-1 and IL-8). These mediators are believed to be involved in the immunological switch of endothelial cells from a normal anti-thrombotic to a pro-thrombotic state. (B) Following P. gingivalis invasion/activation of vascular endothelial cells, these cells recruit monocytes, and, in the presence of elevated circulating lipids such as ox-LDL, atheroma forms.
