P. gingivalis W83 Mediates Inflammatory Changes in NEMO^EC-iKO ApoE^-/- Mice Aortas

Objectives: P. gingivalis (Pg) is an established etiological agent of a variety of extraoral infections, especially those of the cardiovascular system and is implicated in the initiation and/or progression of atherosclerotic cardiovascular disease (ACD). Endothelial cells are likely involved not only in the initiation and progression of cardiovascular diseases (CVDs) such as ACD but also in periodontal disease. Some Pg strains can invade various types of endothelial cells and cause dysfunction of these cells, similar to that known to occur in human ACD. Since inflammation has a major role in ACD, as well as in periodontal disease (PD), we sought to determine the effects of Pg in the absence of NF-κβ by deletion of NF-κβ essential modulator (NEMO) in vivo.
Methods: ApoE^-/- mice with endothelial-specific ablation of NEMO (NEMO^EC-iKO/ApoE^-/- ) were used in this study. Animals were randomly grouped into 6 groups and were orally infected over 6 weeks with Pg W83 or Δ717 (isogenic mutant incapable of stimulation of autophagy in host cells) or sterile vehicle. The heart tissues were then collected from all mice and RNA was isolated. Using the nanostring nCounter platform, which enables direct multiplexed measurement of gene expression, we determined the Pg infection-associated specific changes in the aortic tissues.
Results: We observed differential expression in the genes involved in the inflammatory process in both P.gingivalis W83 and Δ717 infected NEMO^EC-iKO/ApoE^-/ mice. However there were contrasting differences between W83 infected, Δ717 infected and sham-infected mice, especially in expression of chemokines (CCR2, CCL5), a transcription factor (jun) and map kinase signaling molecules (MKK6, MKK3/6).
Conclusions: Our results indicate that P.gingvalis W83 infection creates characteristic changes in the aortic inflammatory response in cells unable to mount a classic inflammatory response and some of these changes depend on the ability of Pg to induce autophagy in the host cells.