on January 22, 2002
Circulation. 2002
Published online before print January 22, 2002, doi: 10.1161/hc0702.104178
Published online before print January 22, 2002, doi: 10.1161/hc0702.104178
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Submitted on November 20, 2001
From the Department of Periodontology and Oral Biology (L.L., E.L.B., S.A.), School of Dental Medicine, Boston University, and Massachusetts General Hospital (E.M., R.A.L.), Boston, Mass. * To whom correspondence should be addressed. E-mail: samar{at}bu.edu.
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 with Porphyromonas 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 live Pg (107 CFU) 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, Pg 16S 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 in Pg-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 with Pg than in noninoculated mice (P<0.001) and was 2-fold greater in Pg-inoculated versus noninoculated high-fat diet--fed mice (P<0.001); all atherosclerotic lesions were macrophage-rich. Pg ribosomal DNA was found in the aortas, livers, and hearts 24 weeks after inoculation. Conclusions—These results provide evidence that long-term systemic challenge with Porphyromonas gingivalis, an oral pathogen, can accelerate atherogenic plaque progression.
Revised on December 11, 2001
Accepted on December 19, 2001
Porphyromonas
gingivalis Infection Accelerates the Progression of
Atherosclerosis in a Heterozygous Apolipoprotein
E--Deficient Murine Model
Key words: atherosclerosis • infection • cardiovascular diseases • Porphyromonas gingivalis
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