NYMC Faculty Publications
Interleukin-1 Receptor Signaling Mediates Atherosclerosis Associated With Bacterial Exposure and/or a High-Fat Diet in a Murine Apolipoprotein E Heterozygote Model: Pharmacotherapeutic Implications
Author Type(s)
Faculty
Additional Author Affiliation
Touro College of Dental Medicine at NYMC
DOI
10.1161/01.CIR.0000142085.39015.31
Journal Title
Circulation
First Page
1678
Last Page
1685
Document Type
Article
Publication Date
9-21-2004
Department
Pharmacology
Abstract
BACKGROUND: Current data demonstrate that progressive atherosclerosis is associated with activation of the inflammatory process, as evidenced by systemic elevations of molecules such as tumor necrosis factor, interleukin (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 (IL-1R1) signaling plays a crucial role in bacteria- and/or high-fat diet (HFD)-enhanced atherogenesis.
METHODS AND RESULTS: Ten-week-old ApoE+/- mice lacking either 1 IL-1R1 allele (ApoE+/-/IL-1R1+/-) or 2 IL-1R1 alleles (ApoE+/-/IL-1R1-/-) fed either an HFD or regular chow were inoculated intravenously with live Porphyromonas gingivalis (P gingivalis) (10(7) CFU), an important periodontal pathogen, or vehicle once per week for 14 or 24 consecutive weeks. Histomorphometry of plaque cross-sectional area in the proximal aortas, en face measurement of plaque area over the aortic trees, and ELISA for systemic proinflammatory mediators were performed. Atherosclerotic lesions of proximal aortas and aortic tree were substantially reduced in ApoE+/-/IL-1R1-/- mice than in ApoE+/-/IL-1R1+/- mice challenged with P gingivalis. At 24 weeks after P gingivalis inoculation, proximal aortic lesion size quantified by histomorphometry was 5-fold-reduced in chow-fed ApoE+/-/IL-1R1-/- mice than in ApoE+/-/IL-1R1+/- mice (P
CONCLUSIONS: Ablation of IL-1R1 under P gingivalis challenge and/or an HFD reduced the progression of atherosclerotic plaques. These results indicate that IL-1 plays a crucial role in bacteria- and/or HFD-enhanced atherogenesis.
Recommended Citation
Chi, H., Messas, E., Levine, R., Graves, D., & Amar, S. (2004). Interleukin-1 Receptor Signaling Mediates Atherosclerosis Associated With Bacterial Exposure and/or a High-Fat Diet in a Murine Apolipoprotein E Heterozygote Model: Pharmacotherapeutic Implications. Circulation, 110 (12), 1678-1685. https://doi.org/10.1161/01.CIR.0000142085.39015.31
