title: Promotion of atherosclerosis by Helicobacter cinaedi infection that involves macrophage-driven proinflammatory responses.
abstract: Helicobacter cinaedi is the most common enterohepatic Helicobacter species that causes bacteremia in humans, but its pathogenicity is unclear. Here, we investigated the possible association of H. cinaedi with atherosclerosis in vivo and in vitro. We found that H. cinaedi infection significantly enhanced atherosclerosis in hyperlipidaemic mice. Aortic root lesions in infected mice showed increased accumulation of neutrophils and F4/80(+) foam cells, which was due, at least partly, to bacteria-mediated increased expression of proinflammatory genes. Although infection was asymptomatic, detection of cytolethal distending toxin RNA of H. cinaedi indicated aorta infection. H. cinaedi infection altered expression of cholesterol receptors and transporters in cultured macrophages and caused foam cell formation. Also, infection induced differentiation of THP-1 monocytes. These data provide the first evidence of a pathogenic role of H. cinaedi in atherosclerosis in experimental models, thereby justifying additional investigations of the possible role of enterohepatic Helicobacter spp. in atherosclerosis and cardiovascular disease.
authors.affiliation: 1] Gladstone Institutes, University of California, San Francisco, CA 94158 [2].
authors.forename: Shahzada
authors.initials: S
authors.lastname: Khan
authors.affiliation: 1] Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan [2].
authors.forename: H N Ashiqur
authors.initials: HN
authors.lastname: Rahman
authors.affiliation: 1] Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan [2].
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matsunaga
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sawa
authors.affiliation: Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshitake
authors.affiliation: Chemistry Department, Sonoma State University, CA 94928.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ono
authors.affiliation: Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Khandaker Ahtesham
authors.initials: KA
authors.lastname: Ahmed
authors.affiliation: Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Md Mizanur
authors.initials: MM
authors.lastname: Rahaman
authors.affiliation: Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Kohta
authors.initials: K
authors.lastname: Oyama
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.affiliation: Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ida
authors.affiliation: Department of Microbiology, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawamura
authors.affiliation: Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Shigemoto
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Akaike
mesh_terms: D000818:Animals; D001011:Aorta / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D050197:Atherosclerosis / Q000382:microbiology* / Q000473:pathology; D002318:Cardiovascular Diseases / Q000382:microbiology* / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D004269:DNA, Bacterial / Q000032:analysis; D005487:Foam Cells / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D006949:Hyperlipidemias / Q000382:microbiology; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D012329:RNA, Bacterial / Q000032:analysis; D011973:Receptors, LDL / Q000096:biosynthesis
chemical_list: D004269:DNA, Bacterial; D012329:RNA, Bacterial; D011973:Receptors, LDL; D052250:Nitric Oxide Synthase Type III
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