The purpose of this molecular epidemiological study is to elucidate, with representative populations of US adults, mechanisms of systemic inflammatory response that are associated with elevated risk of cardiovascular disease (CVD) observed among persons with periodontal disease. This nested cross-sectional study will select subjects from the existing Atherosclerosis Risk in Communities (ARIC) study, an ongoing longitudinal cohort study of a random sample of 16,000 people aged 45-64 years in four states. Existing records of clinical periodontal status from the ARIC study will be used to study equal number of subjects across categories of probing pocket depth (PPD) extent scores. Stored serum samples will be analyzed by ELISA for C-reactive protein (CRP- a non-specific acute phase-reactant) and for lipopolysaccharide binding protein (LBP- an endogenous carrier molecule that binds LPS to the CD14 receptor of polymorphonuclear leukocytes, enhancing the release of inflammatory mediators). Those data will be linked to existing ultrasound measurements of intimal wall thickness of the carotid and popliteal arteries, physician diagnoses of acute CVD events, and other risk factors collected in the ARIC study. In addition, data currently are being collected (with no cost to this project) from assays of inflammatory mediators (IL-6, IL-10 and TNFalpha) in gingival crevicular fluid (GCF) and serum in the same subjects. Statistical analyses will evaluate key components of our hypothesized model of periodontal-CVD etiology. Relationships between extent of PPD and GCF inflammatory mediators will be evaluated using least squares regression models that control for other intra-oral conditions and socio-demographic variables. Severity (mean levels) and prevalence (thresholds of clinically meaningful elevation) of serum inflammatory mediators (CRP, IL-6, IL-10 and TNFalpha) will be compared between PPD groups controlling for other mediators (CRP, IL-6, IL-10 and TNFalpha) will be compared between PPD groups controlling for other systemic diseases. Finally, the multivariate models will assess hypothesized synergistic effects between periodontal disease and serum LBP on systemic inflammatory mediators and prevalent CVD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Comprehensive Center (P60)
Project #
1P60DE013079-01
Application #
6156424
Study Section
Project Start
1999-08-01
Project End
2000-07-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Arce, R M; Caron, K M; Barros, S P et al. (2012) Toll-like receptor 4 mediates intrauterine growth restriction after systemic Campylobacter rectus infection in mice. Mol Oral Microbiol 27:373-81
Qian, Li; Wu, Hung-ming; Chen, Shih-Heng et al. (2011) ?2-adrenergic receptor activation prevents rodent dopaminergic neurotoxicity by inhibiting microglia via a novel signaling pathway. J Immunol 186:4443-54
Arce, R M; Diaz, P I; Barros, S P et al. (2010) Characterization of the invasive and inflammatory traits of oral Campylobacter rectus in a murine model of fetoplacental growth restriction and in trophoblast cultures. J Reprod Immunol 84:145-53
Maile, Laura A; Busby, Walker H; Nichols, Timothy C et al. (2010) A monoclonal antibody against alphaVbeta3 integrin inhibits development of atherosclerotic lesions in diabetic pigs. Sci Transl Med 2:18ra11
Light, Kathleen C; Bragdon, Edith E; Grewen, Karen M et al. (2009) Adrenergic dysregulation and pain with and without acute beta-blockade in women with fibromyalgia and temporomandibular disorder. J Pain 10:542-52
Lemmon, Christopher A; Chen, Christopher S; Romer, Lewis H (2009) Cell traction forces direct fibronectin matrix assembly. Biophys J 96:729-38
Qian, Li; Hu, Xiaoming; Zhang, Dan et al. (2009) beta2 Adrenergic receptor activation induces microglial NADPH oxidase activation and dopaminergic neurotoxicity through an ERK-dependent/protein kinase A-independent pathway. Glia 57:1600-9
Williams, Ray C (2008) Understanding and managing periodontal diseases: a notable past, a promising future. J Periodontol 79:1552-9
Qian, Li; Wei, Sung-Jen; Zhang, Dan et al. (2008) Potent anti-inflammatory and neuroprotective effects of TGF-beta1 are mediated through the inhibition of ERK and p47phox-Ser345 phosphorylation and translocation in microglia. J Immunol 181:660-8
Qian, Li; Flood, Patrick M (2008) Microglial cells and Parkinson's disease. Immunol Res 41:155-64

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