Pathogen-accelerated atherosclerosis occurs early after exposure and can be prevented via immunization
Date
2004
DOI
Authors
Miyamoto, Takanari
Version
OA Version
Citation
Abstract
Accumulating evidence suggests that specific infectious agents such as Porphyromonas gingivalis may accelerate atherosclerosis in both human and animal studies. However, several recent clinical studies to define the early events associated with pathogen-accelerated atherosclerosis have reported negative results on progression of atherosclerosis following treatment of patients with antibiotics. Their results suggest that infection may contribute to early atherosclerosis which might be associated with chronic inflammation and atherosclerosis at an early stage. In this study, apolipoprotein E-deficient (ApoE[-/-]mice were either challenged with P. gingivalis or an invasive-impaired P. gingivalis fimbriae-deficient mutant (FimA-) or immunized with a heat-killed P. gingivalis preparation prior to oral challenge with P. gingivalis and the inflammatory response and atheroma deposition in the aorta were characterized. Animals were sacrificed 24-hours or 6-weeks after the final bacterial challenge. Serum analysis of all groups of mice (unchallenged, challenged with P. gingivalis, challenged with fimA- mutant and immunized and challenged with P. gingivalis) revealed no differences in interleukin-6 or serum amyloid A between groups. At both time points as evidenced by oil red O staining and immunohistochemistry, mice infected with P. gingivalis but not mice challenged with fimA mutant or immunized and challenged mice presented with increased atheroma formation, evidence of macrophage infiltration, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and Toll-like receptor-2 and -4 in aortic arch tissue. We conclude that invasive P. gingivalis infection accelerates atherosclerosis very early after exposure to this organism likely through a mechanism involving up-regulation of innate immune markers. Furthermore, immunization prior to bacterial challenge presents early inflammatory events and acceleration of atherosclerosis.
Description
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Thesis (M.S.D.)--Boston University Goldman School of Dental Medicine, 2004 (Periodontology and Oral Biology).
Includes bibliography (leaves 41-54).
Thesis (M.S.D.)--Boston University Goldman School of Dental Medicine, 2004 (Periodontology and Oral Biology).
Includes bibliography (leaves 41-54).
License
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.