Periodontitis and atherogenesis in high cholesterol-fed rabbits
Date
2011
DOI
Authors
Abdallah, Rima
Version
OA Version
Citation
Abstract
EpidemioIogicaI and recent clinical studies have implicated periodontitis as a risk factor for cardiovascular disease. The purpose of this study was to determine whether treatment of periodontitis with topical Resolvin E1 (RvE1) reduces the risk for cardiovascular disease in a rabbit modeI of periodontitis and atherosclerosis. Periodontitis was induced using ligature and Porphyromonas gingivalis (P. gingivalis) for the first 6-weeks in 39 animals on a 13 week regimen of 0.5% cholesterol diet, whiIe 2 animaIs were placed on regular chow and served as control. Simultaneously, the animals were divided into 4 study groups and received no treatment; vehicle (5% ethanol in PBS); RvE1 (1 mg/ml in 5% ethanol), or; RvEl (0.1 mg/ml in 5% ethanol) starting at the time of disease induction which was the first day of the study. In addition, a group of animals received ligature and cholesterol diet without P. gingivalis and followed the same experimental plan. Experiments were conducted on an every-other-day schedule. P. gingivalis was stopped at 6 weeks while the assigned treatments continued for 13 weeks until the end of the study. At 13 weeks, all animals were sacrificed and morphometric, radiographic and histologic evaluations were performed. Histologic sections were stained with Hematoxylin-eosin (H&E) and Masson’s trichrome for histomorphometry and descriptive histology. Lipid deposition (fatty streaks) was evaluated by computer-assisted morphometry in the aortas en face after staining with Sudan IV, and on H&E stained sections. Clinical and radiographic measurements of the harvested mandibles revealed significant periodontal inflammation characterized by attachment and bone loss in vehicle and untreated groups at 13 weeks, while RvE1 treatment prevented periodontal inflammation and bone loss induced by P. ghgivalis in a dose dependent manner. Histomorphometric measurements showed similar findings; RVE1 treated animals demonstrated significantly less bone loss compared to periodontitis and vehicle groups. Levels of total serum cholesterol, HDL, LDL and triglycerides significantly increased in all animaIs on a cholesterol diet at 13 weeks (P<0.001). There were no significant weight changes. As expected, the animals receiving only cholesterol diet demonstrated significant atherogenic changes indicated by lipid deposition in the aorta. Interestingly, periodontal disease significantly increased aortic lipid deposition compared to Iigature alone, independent of increased circulating lipid levels. AnimaIs receiving RvE1 treatment did not exhibit lipid deposition despite the P. gingivalis application. RvE1 treatment prevented the atherogenic changes associated with periodontal inflammation; lipid deposition was at similar levels to the ligature alone group, indicating the role of inflammation in atherosclerosis. Similarly, in the absence of local periodontal inflammation, oral topical application of RvE1 resulted in significantly less lipid deposition compared to the untreated and vehicle groups suggesting that topically applied RvE1 is absorbed and exerts a direct systemic action in atherogenesis induced by the high cholesterol diet. Histopathological analysis revealed less inflammatory cell infiltration and a lower intima/media ratio indicating less inflammation in the aortas of animals treated with RvE1. In an experimental model of periodontitis and atherogenesis, RvE1 , used as a topical agent, resulted in prevention of atherosclerotic changes as well as periodontal bone loss induced by P. gingivalis. Interestingly, topically administered RvEI provided protection from atherogenic changes in the 0.5% cholesterol-fed rabbits. These results show the potential benefits of RvE1 treatment in the prevention of atherogenic changes in the aorta suggesting that RvE1 can impact macrophage infiltration into intima. The results of the present study warrant further investigation of the mechanism of action of RvEl and its potential use as a therapeutic agent in local and systemic diseases characterized by chronic inflammation.
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Dissertation (DSc) -- Boston University, Henry M. Goldman School of Dental Medicine, 2011 (Department of Periodontology and Oral Biology).
Includes bibliographic references: leaves 150-188.
Dissertation (DSc) -- Boston University, Henry M. Goldman School of Dental Medicine, 2011 (Department of Periodontology and Oral Biology).
Includes bibliographic references: leaves 150-188.
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This work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.