Atherosclerotic vascular disease (ASVD) is the leading cause of death in developed countries. Although there are numerous recognized risk factors for ASVD, including hypertension, hyperlipidemia, diabetes, cigarette smoking, and genetics, approximately one half of all ASVD deaths cannot be attributed to these risk factors. Periodontal disease (PD) is recognized as a risk factor for ASVD independent of other known risk factors, and has been suggested as a cause of ASVD in cases lacking traditional risk factors. PD is a microbial-induced inflammatory disease of the tissues surrounding and supporting the teeth, which can lead to tooth loss. The oral cavity is inhabited by more than 650 species of bacteria, but only a select few are implicated in development of periodontal disease. Four of these select species are Porphyromonas gingivalis (Pg), Treponema denticola (Td), Tanerella forsythia (Tf) and Fusobacterium nucleatum (Fn). Evidence supporting the association between ASVD and PD includes epidemiological studies and detection of components of these four bacteria (as well as of other oral microbes) within human atherosclerotic plaque samples. However, there is not sufficient evidence to declare a causal relationship between PD and ASVD. It is not clear if the bacterial components detected in plaque were from viable bacteria causing active infection, or from dead bacteria caught in plaque as bystanders. Atherosclerosis-prone ApoEnull mice and periodontitis-prone integrin ?6-/- mice will be chronically orally infected with Pg+Td+Tf+Fn for 24 weeks, and upon sacrifice will be examined for evidence of periodontal disease, bacteremia and atherosclerosis (Aims 1 and 3). This mouse model is designed to demonstrate successful induction of periodontal disease, natural systemic spread of periodontal pathogens, and induction of plaque formation. Presence of live bacteria in the aortic wall will be detected, and an immune response to the bacteria within the aortic wall and atherosclerotic plaque will be determined (Aim 2). The objective of this study is to demonstrate that periodontal pathogenic bacteria are directly involved in atherosclerosis formation by actively invading vessel walls and exacerbating the innate immune response. Additionally, we will develop the integrin ?6-/- mouse as a model of periodontal disease and systemic disease more closely resembling the human diseases. The data from these studies will strengthen the evidence for a direct association between PD and ASVD, and will emphasize the importance of maintaining oral health for overall systemic health.

Public Health Relevance

Cardiovascular disease (CVD) is the leading cause of death in developed countries, but not all causes of CVD are known. People who have gum disease have a higher risk for developing CVD, yet there is no evidence that gum disease directly causes CVD. This study aims to demonstrate that gum disease plays a direct role in developing CVD using a mouse model of chronic gum disease and CVD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DE023492-01
Application #
8521695
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Frieden, Leslie A
Project Start
2013-08-16
Project End
2016-08-15
Budget Start
2013-08-16
Budget End
2014-08-15
Support Year
1
Fiscal Year
2013
Total Cost
$35,647
Indirect Cost
Name
University of Florida
Department
Dentistry
Type
Schools of Dentistry
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611