Published online before print May 3, 2004, doi: 10.1161/01.CIR.0000129769.17895.F0
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(Circulation. 2004;109:2801-2806.)
© 2004 American Heart Association, Inc.
Basic Science Reports |
Innate Immune Recognition of Invasive Bacteria Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice
From the Department of Medicine, Section of Infectious Diseases, Boston University Medical Center, Boston, Mass (F.C.G., H.-H.C., H.Y., C.A.G.); Department of Endodontics, Goldman School of Dental Medicine, Boston, Mass (C.H.); School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan (H.-H.C.); Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass (J.C.); Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim, Norway (E.L.); Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Mass (E.L.); Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston, Mass (J.W., C.A.G.); and Department of Microbiology, Boston University School of Medicine, Boston, Mass (C.A.G.).
Correspondence to Dr Caroline Attardo Genco, EBRC, Room 637, 650 Albany St, Boston, MA 02118. E-mail caroline.genco{at}bmc.org
Received October 14, 2003; revision received February 5, 2004; accepted February 13, 2004.
Background— Infectious diseases have emerged as potential risk factors for cardiovascular disease (CVD). Epidemiological studies support a connection between periodontal disease, a chronic inflammatory disease of the supporting tissues of the teeth, and CVD.
Methods and Results— To directly test the connection between periodontal disease and atherosclerosis, apoE–/– mice were orally challenged with the periodontal disease pathogen Porphyromonas gingivalis or an invasion-impaired P gingivalis fimbriae-deficient mutant (FimA–). Both wild-type P gingivalis and the FimA– mutant were detected in blood and aortic arch tissue of apoE–/– mice by PCR after challenge. ApoE–/– mice challenged with wild-type P gingivalis presented with increased atherosclerotic plaque and expressed the innate immune response markers Toll-like receptor (TLR)-2 and TLR-4 in aortic tissue. Despite detection of the FimA– mutant in the blood and in aortic arch tissue, apoE–/– mice challenged with the FimA– mutant did not present with periodontal disease, upregulation of TLRs, or accelerated atherosclerosis. Furthermore, we demonstrate that immunization to control P gingivalis-elicited periodontal disease concomitantly prevents P gingivalis-accelerated atherosclerosis.
Conclusions— We conclude that invasive P gingivalis accelerates atherosclerosis.
Key Words: infection • inflammation • atherosclerosis • receptors • endothelium
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