Invasion of Oral and Aortic Tissues by Oral Spirochete Treponema denticola in ApoE−/−Mice Causally Links Periodontal Disease and Atherosclerosis

Abstract

ABSTRACTTreponema denticolais a predominantly subgingival oral spirochete closely associated with periodontal disease and has been detected in atherosclerosis. This study was designed to evaluate causative links between periodontal disease induced by chronic oralT. denticolainfection and atherosclerosis in hyperlipidemic ApoE−/−mice. ApoE−/−mice (n= 24) were orally infected withT. denticolaATCC 35404 and were euthanized after 12 and 24 weeks.T. denticolagenomic DNA was detected in oral plaque samples, indicating colonization of the oral cavity. Infection elicited significantly (P= 0.0172) higher IgG antibody levels and enhanced intrabony defects than sham infection.T. denticola-infected mice had higher levels of horizontal alveolar bone resorption than sham-infected mice and an associated significant increase in aortic plaque area (P≤ 0.05). Increased atherosclerotic plaque correlated with reduced serum nitric oxide (NO) levels and increased serum-oxidized low-density lipoprotein (LDL) levels compared to those of sham-infected mice.T. denticolainfection altered the expression of genes known to be involved in atherosclerotic development, including the leukocyte/endothelial cell adhesion gene (Thbs4), the connective tissue growth factor gene (Ctgf), and the selectin-E gene (Sele). Fluorescentin situhybridization (FISH) revealedT. denticolaclusters in both gingival and aortic tissue of infected mice. This is the first study examining the potential causative role of chronicT. denticolaperiodontal infection and vascular atherosclerosisin vivoin hyperlipidemic ApoE−/−mice.T. denticolais closely associated with periodontal disease and the rapid progression of atheroma in ApoE−/−mice. These studies confirm a causal link for active oralT. denticolainfection with both atheroma and periodontal disease.