RvE1 Reduces Periodontitis Induced Atherosclerotic Changes in Rabbits

Periodontitis exacerbates atherogenic changes in the aorta of rabbits.  RvE1, an agonist of resolution of inflammation, was shown to prevent and reverse periodontal disease promoting regeneration of lost tissues. The purpose of this study was to determine the impact of topically applied RvE1 on atherogenic diet induced lipid deposition in the aorta of rabbits with and without periodontitis.

Methods:

Rabbits (n=39) were fed a 13-week regimen of 0.5% cholesterol diet; 2 animals received normal rabbit chow. Periodontitis was induced with silk ligature and 3x/week application of Porphyromonas gingivalis (P.gingivalis.).  Simultaneous treatments were performed 3x/week for 13 weeks in 9 groups; 1- ligature alone, 2- ligature + P.gingivalis., 3- ligature + P.gingivalis + vehicle, 4- ligature + P.gingivalis. + RvE1 (0.4 µg), 5- ligature + P.gingivalis. + RvE1 (4.0 µg), 6- ligature + vehicle, 7- ligature + RvE1 (0.4 µg), 8- ligature + RvE1 (4.0 µg), normal diet alone.  Periodontitis was quantified morphologically and histologically.  Aortic lipid deposition was evaluated en face after staining with Sudan IV. Hematoxylin-eosin stained sections were analyzed for inflammatory cell infiltration in intima and media layers. High field ex vivo MR images of aortic segments were further evaluated for atherosclerotic changes.

Results:

Significant atherogenic changes characterized by fatty streaks were detected in rabbits receiving atherogenic diet and exacerbated by periodontitis.  Oral topical RvE1 significantly prevented periodontitis and atherogenesis dose dependently (p<0.05).  RvE1 prevented intima and media widening and inflammatory cell infiltration. Ex vivo MRI images demonstrated RvE1 prevented early stage plaque formation.

Conclusions:

Topical RvE1 protected from atherogenic changes induced by periodontitis.  In the absence of periodontitis, oral topical RvE1 protected from atherogenic changes induced by diet.  Taken together, the data suggest that periodontitis exacerbates atherogenesis; RvE1 protects from periodontitis induced atherogenic changes, and in the absence of periodontitis, RvE1 provides significant protection against atherogenesis.