Abstract 14157: Periodontal Microbiome Induces Inflammation and Atherosclerosis in Hyperlipidemic Atherogenic ApoeNull Mice
Introduction: Periodontal disease (PD) is a polymicrobial dysbiotic chronic inflammatory disease produced by a complex subgingival microbiome, and is linked to systemic inflammatory atherosclerotic vascular disease (ASVD). American Heart Association supported the association between PD and ASVD but not causal association. Prior reports investigated the associations between these two diseases PD and ASVD. But the complex signaling molecules and mechanisms establishing a causal association are not well defined.
Methods: To investigate how polybacterial infections initiate atherosclerotic plaque growth, ApoEnull mice were orally infected with a polybacterial consortium of 4 well-characterized periodontal pathogens Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum. We assessed PD characteristics, hematogenous dissemination of bacteria, peripheral T cell response, serum inflammatory cytokines, atherosclerosis risk factors, atherosclerotic plaque development, and alteration of aortic gene expression.
Results: Polybacterial infections have enhanced gingival colonization and significantly induced alveolar bone loss ApoEnull mice. Polybacterial infections were found to be invasive with hematogenous dissemination into heart and aorta. Polybacterial infection-induced significantly higher levels of serum risk factors (oxidized LDL, nitric oxide), altered lipid profiles (cholesterol, triglycerides, chylomicrons, VLDL) as well as accelerated aortic plaque formation in ApoEnull mice. Polybacterial infection is associated with significant decreases in Apoa1, Apob, Birc3, Fga, FgB genes that are associated with atherosclerosis. Gingival infections after 12 weeks had modified levels of inflammatory molecules, with decreased Fas ligand, IL-13, SDF-1 and increased chemokine RANTES. At 24 weeks of chronic infection additional changes in inflammatory molecules were induced with reduced KC, MCSF, and enhanced GM-CSF, IFNγ, IL-1β, IL-13, IL-4, IL-13, lymphotactin, and RANTES.
Conclusions: This is the first study demonstrating differences in the host immune response to a polybacterial infection with atherosclerotic lesion progression in a mouse model.
Author Disclosures: S. Chukkapalli: None. I. Velsko: None. M. Rivera-Kweh: None. D. Zheng: None. A. Lucas: None. K. Lakshmyya: None.
- © 2015 by American Heart Association, Inc.