title: Osteoprotegerin Prevents Development of Abdominal Aortic Aneurysms.
abstract: Abdominal aortic aneurysms (AAAs), which commonly occur among elderly individuals, are accompanied by a risk of rupture and subsequent high mortality. Establishment of medical therapies for the prevention of AAAs requires further understanding of the molecular pathogenesis of this condition. This report details the possible involvement of Osteoprotegerin (OPG) in the prevention of AAAs through inhibition of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In CaCl2-induced AAA models, both internal and external diameters were significantly increased with destruction of elastic fibers in the media in Opg knockout (KO) mice, as compared to wild-type mice. Moreover, up-regulation of TRAIL expression was observed in the media by immunohistochemical analyses. Using a culture system, both the TRAIL-induced expression of matrix metalloproteinase-9 in smooth muscle cells (SMCs) and the chemoattractive effect of TRAIL on SMCs were inhibited by OPG. These data suggest that Opg may play a preventive role in the development of AAA through its antagonistic effect on Trail.
authors.affiliation: Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Batmunkh
authors.initials: B
authors.lastname: Bumdelger
authors.affiliation: Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kokubo
authors.affiliation: Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kamata
authors.affiliation: Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Department of Surgery and Clinical Science, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Cardiovascular Research Institute, Kurume University, Kurume, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Aoki
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Orita
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Environmetrics and Biometrics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: Megu
authors.initials: M
authors.lastname: Ohtaki
authors.affiliation: Department of Forensic Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Nagao
authors.affiliation: Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Ishida
authors.affiliation: Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Yoshizumi
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D002122:Calcium Chloride / Q000009:adverse effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000473:pathology; D055786:Gene Knockout Techniques; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D000199:Actins; D053244:Osteoprotegerin; D053221:TNF-Related Apoptosis-Inducing Ligand; C506031:Tnfrsf11b protein, mouse; C505654:Tnfsf10 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D002122:Calcium Chloride