Promotion of atherosclerosis by Helicobacter cinaedi infection that involves macrophage-driven proinflammatory responses

• Published in: Scientific reports 2014-04, Vol.4 (1), p.4680, Article 4680
• Main Authors: Khan, Shahzada, Rahman, H. N. Ashiqur, Okamoto, Tatsuya, Matsunaga, Tetsuro, Fujiwara, Yukio, Sawa, Tomohiro, Yoshitake, Jun, Ono, Katsuhiko, Ahmed, Khandaker Ahtesham, Rahaman, Md Mizanur, Oyama, Kohta, Takeya, Motohiro, Ida, Tomoaki, Kawamura, Yoshiaki, Fujii, Shigemoto, Akaike, Takaaki
• Format: Article
• Language: English
• Subjects: 13; 13/51; 631/326/41; 64; 64/60; 692/699/75/593; 82; 96/21; Animal models; Animals; Aorta; Aorta - immunology; Aorta - microbiology; Aorta - pathology; Arteriosclerosis; Atherosclerosis; Atherosclerosis - microbiology; Atherosclerosis - pathology; Bacteremia; Cardiovascular Diseases - microbiology; Cardiovascular Diseases - pathology; Cell Differentiation - immunology; Cells, Cultured; Cholesterol; Cytolethal distending toxin; DNA, Bacterial - analysis; Foam Cells - immunology; Helicobacter Infections - immunology; Helicobacter Infections - microbiology; Helicobacter pylori - genetics; Helicobacter pylori - immunology; Helicobacter pylori - pathogenicity; Humanities and Social Sciences; Hyperlipidemias - microbiology; Infections; Inflammation; Inflammation - immunology; Leukocytes (neutrophilic); Macrophages; Macrophages - immunology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes; Monocytes - immunology; multidisciplinary; Neutrophils - immunology; Nitric Oxide Synthase Type III - genetics; Pathogenicity; Receptors, LDL - biosynthesis; Ribonucleic acid; RNA; RNA, Bacterial - analysis; Rodents; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep04680

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.