<b> <i>Porphyromonas gingivalis</i> </b> Infection Accelerates the Progression of Atherosclerosis in a Heterozygous Apolipoprotein E–Deficient Murine Model

TLDR

Periodontitis can disseminate systemically and is linked to accelerated atherosclerosis. The study tested whether repeated systemic inoculations of Porphyromonas gingivalis accelerate atherosclerosis in heterozygous ApoE‑deficient mice. Mice received weekly intravenous Pg or vehicle for up to 24 weeks, and plaque burden was quantified by histomorphometry, en face analysis, PCR for Pg DNA, ELISA for inflammatory mediators, and macrophage immunolocalization. Pg‑challenged mice developed larger, macrophage‑rich aortic lesions earlier and up to nine‑fold greater at 24 weeks, with Pg DNA detected in aortas, livers, and hearts, confirming that chronic Pg exposure accelerates plaque progression.

Abstract

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.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.These results provide evidence that long-term systemic challenge with Porphyromonas gingivalis, an oral pathogen, can accelerate atherogenic plaque progression.