Affiliation:
1. 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.
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 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
(10
7
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
373 articles.
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