Chi, Hunghui2019-12-162019-12-1620042004(OCoLC)234286695(OCoLC)234286695b2787316xhttps://hdl.handle.net/2144/38866PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.Thesis (M.S.D.)--Boston University, Henry M. Goldman School of Dental Medicine, 2004 (Periodontology and Oral Biology).Includes bibliographical references (leaves 33-52).Background: Current data demonstrate that progressive atherosclerosis is associated with activation of the inflammatory process, as evidenced by systemic elevation in molecules such as TNF, IL-6 and IL-1. It has been postulated that inflammatory events within an atherogenic lesion are induced by oxidized LDL. Recent evidence suggests that infectious agents including those that cause periodontal disease may also play an important role. Studies presented here tested the hypothesis that IL-1 receptor signaling plays a crucial role in bacteria- and/or HFD-enanced atherogenesis. Methods and Results: Ten-week-old ApoE[+/-] mice lacking either one IL-1Rl allele (ApoE[+/-]/IL-1R1[+/-]) or the two IL-1Rl alleles (ApoE[+/-]IL-1Rl[-/-]) fed either a HFD or regular chow were inoculated intravenously with live Porphyromonas gingivalis P.g.) (10[7] CFU), an important periodontal pathogen or vehicle once per week for 14 and 24 consecutive weeks. Histomoxphometry of plaque cross-sectional area in the proximal aortas, En Face measurement of plaque area over the aortic trees, and ELISA for systemic proinflamatory mediators were performed. Atherosclerotic lesions of proximal aortas and aortic tree were substantially reduced in ApoE[+/-]/IL-1R1[-/-] mice than ApoE[+/-]/IL-1Rl[+/-] mice challenged with P.g. At 24 weeks after P.g. inoculation, proximal aortic lesion size quantified by histomorphometry was 5-fold reduced in chow-fed ApoE[+/-]/IL-1RI[-/-] mice than ApoE[+/-]/IL-1Rl[+/-] mice (p[less than]0.05).　In HFD, ApoE[+/-]/IL-1R1[-/-] mice exhibited a marked attenuation of the progression of atherosclerotic lesions (78%-97%), with and without P.g. inoculation (p[less than]0.05). Conclusion: Ablation of IL-1 receptor-1 under P.g. challenge and/or HFD reduced the progression of atherosclerotic plaques. These results indicate that IL-1 plays a crucial role in bacteria and/or HFD-enhanced atherogenesis.en-USThis work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.ArteriosclerosisInterleukin-1Thesis/Dissertation