OBJECTIVES: - It has been postulated that systemic infection with pathogens such as Porphyromonas gingivalis (Pg) elevate the inflammatory response and increase susceptibility to atherosclerosis. Doxycycline has been known to be a pluripotent drug affecting several cell functions. In particular, it is believed to affect matrix remodeling, an important process involved in the development of atherosclerosis. Thus, we hypothesized that Doxycycline would be beneficial in diet- and/or Pg-induced atherosclerosis.
METHODS: - Apolipoprotein E heterozygous (ApoE+/-) mice were inoculated weekly with Pg and treated with either Doxycycline or saline; animals were fed either a high-fat or normal chow diet. Animals were sacrificed at 14 or 24 weeks and histomorphometric analysis of atheromatous lesions in the proximal aorta and serum cytokine profiling were performed.
RESULTS: Histomorphometric analysis demonstrated that administration of Doxycycline to mice fed a high fat diet and inoculated with Pg resulted in a reduction of mean percentage of proximal aorta occupied by atheromatous plaque lesion from 16.46% +/- 1.69 to 1.141% +/- 0.23 (p<0.05) p="0.106)">
CONCLUSIONS: - Doxycycline inhibits pro-inflammatory cytokines and results in profound reduction in the progression of atherosclerosis in ApoE+/- Pg-inoculated and/or high fat diet fed mice.
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