Gender-Specific Effects of Pgingivalis in Heterozygous ApoE Mice

Men are at higher risk for periodontal and cardiovascular diseases compared to women, although they have lower serum levels of risk markers, including lipids and acute phase proteins. Objectives: In this study, we compared the systemic inflammatory and atherosclerotic response of male and female mice to infection with the periodontal pathogen Porphyromonas gingivalis. Methods: Forty-eight heterozygous Apolipoprotein E-deficient mice (24 males, 24 females) maintained on normal diet were infected twice by intra-subcutaneous chamber injections of P.gingivalis or vehicle at weeks 11 and 14. Serum was collected before the first challenge and bi-weekly thereafter, to quantify levels of HDL-cholesterol and the murine acute phase protein serum amyloid A (SAA). Mice were sacrificed at week 17 to evaluate aorta atheroma lesion score. Factorial ANOVA was used to assess whether the mean baseline HDL-cholesterol and SAA levels, and the average lesion scores were affected by sex and case-status, and whether the difference between control and P.gingivalis-challenged mice was the same for males and females. Changes over time for HDL-cholesterol and SAA levels were assessed using Generalized Estimating Equations (GEE) models. Results: At baseline, males had significantly higher HDL-cholesterol levels (Psex<0.01). Following P.gingivalis-challenge, HDL-cholesterol levels decreased over time in infected males only (Psex-by-time<0.01 and Pcase-by-time=0.04), whereas SAA levels increased and remained elevated over time in both male and female infected mice (Pcase-by-time<0.01). Lesion scores were significantly higher in infected mice (3-fold, Pcase<0.01), and lesion scores of all mice were positively correlated with SAA levels at sacrifice (Spearman correlation coefficient = 0.40, P<0.01). Conclusions: In this murine model of early atheroma, P.gingivalis infection induced sex-specific changes in serum markers of risk for atherosclerosis, although there were no gender differences in atheroma lesion score. This model could be useful to explore human gender-specific differences in susceptibility to periodontal and cardiovascular diseases. Supported by NIDCR grant #DE14459.