title: Sequential colonization of periodontal pathogens in induction of periodontal disease and atherosclerosis in LDLRnull mice.
abstract: Periodontal disease (PD) and atherosclerotic vascular disease (ASVD) are both chronic inflammatory diseases with a polymicrobial etiology and have been epidemiologically associated. The purpose is to examine whether periodontal bacteria that infect the periodontium can also infect vascular tissues and enhance pre-existing early aortic atherosclerotic lesions in LDLRnull mice. Mice were orally infected with intermediate bacterial colonizer Fusobacterium nucleatum for the first 12 weeks followed by late bacterial colonizers (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia) for the remaining 12 weeks mimicking the human oral microbiota ecological colonization. Genomic DNA from all four bacterial was detected in gingival plaque by PCR, consistently demonstrating infection of mouse gingival surfaces. Infected mice had significant levels of IgG and IgM antibodies, alveolar bone resorption, and showed apical migration of junctional epithelium revealing the induction of PD. These results support the ability of oral bacteria to cause PD in mice. Detection of bacterial genomic DNA in systemic organs indicates hematogenous dissemination from the gingival pockets. Bacterial infection did not alter serum lipid fractions or serum amyloid A levels and did not induce aortic atherosclerotic plaque. This is the first study examining the causal role of periodontal bacteria in induction of ASVD in LDLRnull mice.
authors.affiliation: Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610-0424, USA.
authors.forename: Sasanka S
authors.initials: SS
authors.lastname: Chukkapalli
authors.affiliation: Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610-0424, USA.
authors.forename: Meena
authors.initials: M
authors.lastname: Easwaran
authors.affiliation: Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610-0424, USA.
authors.forename: Mercedes F
authors.initials: MF
authors.lastname: Rivera-Kweh
authors.affiliation: Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610-0424, USA.
authors.forename: Irina M
authors.initials: IM
authors.lastname: Velsko
authors.affiliation: Biodesign Institute, Arizona state University, Tempe, AZ 85287-5001, USA.
authors.forename: Sriram
authors.initials: S
authors.lastname: Ambadapadi
authors.affiliation: Division of Periodontics and Dental Hygiene, University of British Columbia, Vancouver, BCV6T 1Z4, Canada.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Dai
authors.affiliation: Division of Periodontics and Dental Hygiene, University of British Columbia, Vancouver, BCV6T 1Z4, Canada.
authors.forename: Hannu
authors.initials: H
authors.lastname: Larjava
authors.affiliation: Biodesign Institute, Arizona state University, Tempe, AZ 85287-5001, USA.
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Lucas
authors.affiliation: Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610-0424, USA.|Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610-0424, USA.
authors.forename: Lakshmyya
authors.initials: L
authors.lastname: Kesavalu
mesh_terms: D016301:Alveolar Bone Loss / Q000209:etiology / Q000473:pathology; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D050197:Atherosclerosis / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D003773:Dental Plaque / Q000382:microbiology / Q000473:pathology; D005881:Gingiva / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D054884:Host-Pathogen Interactions; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010510:Periodontal Diseases / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology; D011973:Receptors, LDL / Q000172:deficiency*
chemical_list: D000907:Antibodies, Bacterial; D008055:Lipids; D011973:Receptors, LDL
keywords: Fusobacterium nucleatum; LDLR−/− mice; Porphyromonas gingivalis; Tannerella forsythia; Treponema denticola; atherosclerosis; periodontal disease; polymicrobial infection