Porphyromonas gingivalisInfection Accelerates the Progression of Atherosclerosis in a Heterozygous Apolipoprotein E–Deficient Murine Model

Abstract

Background— Current epidemiological data suggest that dental infections affecting tooth-supporting tissues (periodontitis) can disseminate into the systemic circulation and thereby contribute to atherosclerosis progression. To test this hypothesis, we investigated the effect of repeated systemic inoculations withPorphyromonas gingivalis(Pg), a putative periodontal pathogen, on the progression of atherosclerosis in heterozygous apolipoprotein E–deficient (ApoE^+/−) mice. Methods and Results— Ten-week-old, male ApoE^+/−mice fed either a high-fat diet or regular chow were inoculated intravenously with livePg(10⁷CFU) or vehicle once per week for 10, 14, or 24 consecutive weeks. Histomorphometry of plaque cross-sectional area in the proximal aortas, en face measurement of plaque area over the aortic trees,Pg16S ribosomal DNA amplification with polymerase chain reaction, ELISA for systemic proinflammatory mediators, and immunolocalization of macrophages in the proximal aorta were performed. Atherosclerotic lesions of the proximal aortas and aortic trees were more advanced inPg-challenged animals than in vehicle control animals and occurred earlier (at 10 weeks) when no lesions were apparent in control animals. At 24 weeks after inoculation, proximal aortic lesion size quantified by histomorphometry was 9-fold greater in chow-fed mice inoculated withPgthan in noninoculated mice (PPg-inoculated versus noninoculated high-fat diet–fed mice (PPgribosomal DNA was found in the aortas, livers, and hearts 24 weeks after inoculation. Conclusions— These results provide evidence that long-term systemic challenge withPorphyromonas gingivalis, an oral pathogen, can accelerate atherogenic plaque progression.