Abstract
The American Heart Association supports an association between periodontal disease (PD) and atherosclerotic vascular disease (ASVD) but does not as of yet support a causal relationship. Recently, we have shown that major periodontal pathogens Porphyromonas gingivalis and Treponema denticola are causally associated with acceleration of aortic atherosclerosis in ApoEnull hyperlipidemic mice. The aim of this study was to determine if oral infection with another significant periodontal pathogen Fusobacterium nucleatum can accelerate aortic inflammation and atherosclerosis in the aortic artery of ApoEnull mice. ApoEnull mice (n = 23) were orally infected with F. nucleatum ATCC 49256 and euthanized at 12 and 24 weeks. Periodontal disease assessments including F. nucleatum oral colonization, gingival inflammation, immune response, intrabony defects, and alveolar bone resorption were evaluated. Systemic organs were evaluated for infection, aortic sections were examined for atherosclerosis, and inflammatory markers were measured. Chronic oral infection established F. nucleatum colonization in the oral cavity, induced significant humoral IgG (P=0.0001) and IgM (P=0.001) antibody response (12 and 24 weeks), and resulted in significant (P=0.0001) alveolar bone resorption and intrabony defects. F. nucleatum genomic DNA was detected in systemic organs (heart, aorta, liver, kidney, lung) indicating bacteremia. Aortic atherosclerotic plaque area was measured and showed a local inflammatory infiltrate revealed the presence of F4/80+ macrophages and CD3+ T cells. Vascular inflammation was detected by enhanced systemic cytokines (CD30L, IL-4, IL-12), oxidized LDL and serum amyloid A, as well as altered serum lipid profile (cholesterol, triglycerides, chylomicrons, VLDL, LDL, HDL), in infected mice and altered aortic gene expression in infected mice. Despite evidence for systemic infection in several organs and modulation of known atherosclerosis risk factors, aortic atherosclerotic lesions were significantly reduced after F. nucleatum infection suggesting a potential protective function for this member of the oral microbiota.
Highlights
Atherosclerotic vascular diseases (ASVD) are the leading cause of death globally [1]
F. nucleatum genomic DNA was detected in the oral cavity of 19 out of 24 mice by the first infection (Table 1) and all mice tested positive for F. nucleatum after at least one infection during the infection period
It is possible that the sampling technique was not sensitive enough to detect subgingival F. nucleatum, which may explain why not all mice had consistently positive samples
Summary
Atherosclerotic vascular diseases (ASVD) are the leading cause of death globally [1]. There are numerous well-established factors that increase risk for ASVD, including genetic factors, hypertension, hypercholesterolemia and smoking, these do not account for all cases, and microbial infection is considered an important risk factor for ASVD [1]. Periodontal disease (PD) causing infectious oral microbes are commonly detected in atherosclerotic plaques. Periodontal disease is characterized by a chronic polymicrobial biofilm that induces inflammatory response in gingival tissues surrounding and supporting the teeth. We are systematically investigating individual periodontal disease pathogens that have been linked to ASVD by a physiologically relevant model of chronic oral infection in hyperlipidemic ApoEnull mice. Our published studies demonstrated significantly increased atherosclerosis in ApoEnull mice after oral P. gingivalis [4], and T. denticola [5], as well as polybacterial infections [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
