title: Gender differences in systemic inflammation and atheroma formation following Porphyromonas gingivalis infection in heterozygous apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  Men are at higher risk for periodontal and cardiovascular diseases compared with women, although they have lower serum levels of risk markers, including lipids and acute phase proteins. In this study, we investigated whether infection with a major periodontal pathogen, Porphyromonas gingivalis, affected the inflammatory and atherosclerotic response of male and female mice differently.
  
  
  METHODS
  Forty-eight heterozygous apolipoprotein E-deficient mice (24 males and 24 females), maintained on normal diet, were infected twice by intrasubcutaneous chamber injections of P. gingivalis or vehicle at weeks 11 and 14 of age. Serum samples were collected before the first infection and bi-weekly thereafter, to quantify levels of high-density lipoprotein (HDL) cholesterol and the murine acute phase protein, serum amyloid A (SAA). Mice were killed at week 17 to evaluate aortic atheroma lesion score.
  
  
  RESULTS
  Males had significantly higher baseline HDL cholesterol levels (p < 0.01, factorial ANOVA). Following P. gingivalis infection, HDL cholesterol levels decreased over time in infected males only [p < 0.05, generalized estimating equation (GEE)], whereas SAA levels increased and remained elevated over time in both male and female infected mice (p < 0.01, GEE). Lesion scores were significantly higher in infected mice (3-fold, p < 0.01, factorial ANOVA), and lesion scores of all mice were positively correlated with SAA levels at the time of killing (Spearman correlation coefficient = 0.40, p < 0.01).
  
  
  CONCLUSIONS
  In these young mice, P. gingivalis infection induced sex-specific changes in serum lipids but no gender differences in acute phase proteins and atheroma lesion score.
authors.affiliation: Center for Oral and Systemic Diseases, School of Dentistry, University of North Carolina Chapel Hill, Chapel Hill, NC 27599-7450, USA. cchamp@email.unc.edu
authors.forename: C
authors.initials: C
authors.lastname: Champagne
authors.forename: N
authors.initials: N
authors.lastname: Yoshinari
authors.forename: J A
authors.initials: JA
authors.lastname: Oetjen
authors.forename: E L
authors.initials: EL
authors.lastname: Riché
authors.forename: J D
authors.initials: JD
authors.lastname: Beck
authors.forename: S
authors.initials: S
authors.lastname: Offenbacher
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D000818:Animals; D001018:Aortic Diseases / Q000209:etiology / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D016866:Bacteroidaceae Infections / Q000150:complications*; D001835:Body Weight; D008076:Cholesterol, HDL / Q000097:blood; D015169:Colony Count, Microbial; D015194:Diffusion Chambers, Culture; D004195:Disease Models, Animal; D005260:Female; D006579:Heterozygote; D007249:Inflammation / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D016966:Porphyromonas gingivalis / Q000502:physiology*; D011897:Random Allocation; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000032:analysis; D012727:Sex Characteristics; D012737:Sex Factors
chemical_list: D000209:Acute-Phase Proteins; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D000685:Serum Amyloid A Protein