Fig. 4.

Proposed integrated model linking Periodontal Disease, Obesity, and Atherosclerosis

We propose the following integrated model linking Periodontal Disease, Obesity and Atherosclerosis with a foundation built on a foundation of dysregulated innate immunity due to the induction of homotolerance. Homotolerance can be induced either by obesity directly or by exposure to P.gingivalis. However, when obesity is combined with P.gingivalis exposure, we speculated that exacerbates the overall homotolerant state thus having an additive effect and further exacerbating Periodontal Disease. We speculate two potential mechanisms that explain how the long-term consequences of periodontal disease exacerbates Atherosclerosis. First is the induction of homotolerance through a persistent low-level bacteremia or perhaps a transient low-level bacteremia induces a tolerant state within the endothelial cells and Macrophages centered on regions of fatty-streaks/athroma development. Specifically, this results in reduced expression of Toll-like Receptors (TLR), which then leaves these cells susceptible to P. gingivalis invasion and increased adhesion receptor expression via nucleotide oligomerization domain-2 NOD2 receptor signaling. Increased adhesion receptor expression increases the likelihood of macrophages transiting from the blood compartment to the aterial intima. When coupled with a high-fat diet macrophages will uptake cholesterol from Low-desnity lipoprotein via the scavenger receptor. Over time this has been shown to foster conversion of the macrophage to a `Foam' cell and progression of Atherosclerosis. Secondly, there is a potential for a spiking bactermia during dental procedures or flossing that could actually overcome the homotolerance and result in a more traditional inflammatory response and wound healing processes which have been shown to exacerbate Atherosclerosis.