Figure 2: Model of biofilm’s possible role in the pathogenesis of atherosclerosis. This illustration outlines one possible pathway by which bacteria may participate in the pathogenesis of the formation of atherosclerotic plaques. It is possible that not only white blood cells but also bacteria can attach to the areas of endothelial cells within the arteries that have upregulated ICAMs and VCAMs due to hydrodynamic injuries. Once bacteria have attached to these sticky areas, they are committed to biofilm phenotype mode of growth. Biofilm phenotype bacteria quickly produce senescence of the host cells to which they are attached, produce a protective extracellular matrix, and downregulate virulence factors. This leads to a tightly bound polymicrobial community of bacteria producing intense inflammation through the inducement of proinflammatory cytokines such as interleukin 1, interleukin 8, interleukin 6, gamma interferon and tumor necrosing factor alpha. The proinflammatory cytokines produce an oxidative milieu through the production of nonphysiologic levels of myeloperoxidase, reactive oxygen species, lipases, and many other oxidative products. It has been generally agreed that this type of oxidative milieu is sufficient to produce oxidative low density lipoproteins (OxLDL) which, in turn, produce macrophages capable of ingesting these degradated LDLs. Foamy macrophages then deposit in the area incasing the biofilm thus sequestering the biofilm in such a way as to allow some repair. Because of the persistent, intense inflammation produced by the biofilm, the “healing” over the plaque is often fibrotic. Although there is much speculation in this scenario, a biofilm role in the pathogenesis of atherosclerosis sheds light on many of the unanswered questions of atherosclerosis.