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Innate Immune Signaling and Porphyromonas gingivalis-accelerated Atherosclerosis

¹ Department of Medicine, Section of Infectious Diseases, and
⁶ Department of Microbiology, Boston University School of Medicine, Evans Biomedical Research Center, 650 Albany Street, Room 637, Boston, MA 02118, USA;
² Department of Conservative Dentistry, Tokushima University School of Dentistry, Tokushima, Japan;
³ Department of Oral Microbiology, Kanagawa Dental College, 82 Inaokoa-cho, Yokosuka 238-8580, Japan;
⁴ School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; and
⁵ Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University Medical Center, Boston, MA, USA

Correspondence: ^* corresponding author, caroline.genco{at}bmc.org

Periodontal diseases are a group of diseases that lead to erosion of the hard and soft tissues of the periodontium, which, in severe cases, can result in tooth loss. Anecdotal clinical observations have suggested that poor oral health may be associated with poor systemic health; however, only recently have appropriate epidemiological studies been initiated, with defined clinical endpoints of periodontal disease, to address the association of periodontal disease with increased risk for cardiovascular and cerebrovascular disease. Although conflicting reports exist, these epidemiological studies support this connection. Paralleling these epidemiological studies, emerging basic scientific studies also support that infection may represent a risk factor for atherosclerosis. With P. gingivalis as a model pathogen, in vitro studies support that this organism can activate host innate immune responses associated with atherosclerosis, and in vivo studies demonstrate that this organism can accelerate atheroma deposition in animal models. In this review, we focus primarily on the basic scientific studies performed to date which support that infection with bacteria, most notably P. gingivalis, accelerates atherosclerosis. Furthermore, we attempt to bring together these studies to provide an up-to-date framework of emerging theories into the mechanisms underlying periodontal disease and increased risk for atherosclerosis, as well as identify intervention strategies to reduce the incidence of periodontal disease in humans, in an attempt to decrease risk for systemic complications of periodontal disease such as atherosclerotic cardiovascular disease.

Key Words: Porphyromonas gingivalis • periodontal disease • Toll-like receptors • endothelium • innate immunity

Abbreviations: ApoE = apolipoprotein E • CAM = cell adhesion molecule • CMV = cytomegalovirus • HAEC = human aortic endothelial cell • HSP = heat-shock protein • HUVEC = human umbilical vein endothelial cell • ICAM-1 = intracellular adhesion molecule-1 • IFN- = interferon- • IgA = immunoglobulin A • IL = interleukin • LPS = lipopoly-saccharide • LDLR = low-density lipoprotein receptor • MCP-1 = macrophage chemotactic protein-1 • MOI = multiplicity of infection • PAMPs = pathogen-associated microbial products • PGE2 = prostaglandin E2 • RANTES = Regulated on Activation, Normal T Expressed and Secreted • SMC = smooth-muscle cells • TLR = toll-like receptor • TNF- = tumor necrosis factor- • VCAM-1 = vascular cell adhesion molecule-1

Journal of Dental Research, Vol. 85, No. 2, 106-121 (2006)
DOI: 10.1177/154405910608500202


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