Osteoprotegerin Prevents Development of Abdominal Aortic Aneurysms

Batmunkh Bumdelger; Hiroki Kokubo; Ryo Kamata; Masayuki Fujii; Koichi Yoshimura; Hiroki Aoki; Yuichi Orita; Takafumi Ishida; Megu Ohtaki; Masataka Nagao; Mari Ishida; Masao Yoshizumi

doi:10.1371/journal.pone.0147088

Osteoprotegerin Prevents Development of Abdominal Aortic Aneurysms

PLoS One. 2016 Jan 19;11(1):e0147088. doi: 10.1371/journal.pone.0147088. eCollection 2016.

Authors

Affiliations

¹ Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
² Department of Surgery and Clinical Science, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
³ Cardiovascular Research Institute, Kurume University, Kurume, Japan.
⁴ Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁵ Department of Environmetrics and Biometrics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
⁶ Department of Forensic Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / metabolism
Animals
Aortic Aneurysm, Abdominal / chemically induced
Aortic Aneurysm, Abdominal / metabolism*
Aortic Aneurysm, Abdominal / pathology*
Calcium Chloride / adverse effects*
Cells, Cultured
Disease Models, Animal
Elastic Tissue / pathology
Gene Knockout Techniques
Humans
Male
Matrix Metalloproteinase 9 / metabolism
Mice
Myocytes, Smooth Muscle / cytology
Myocytes, Smooth Muscle / metabolism
Osteoprotegerin / genetics
Osteoprotegerin / metabolism*
TNF-Related Apoptosis-Inducing Ligand / metabolism*

Substances

Actins
Osteoprotegerin
TNF-Related Apoptosis-Inducing Ligand
Tnfrsf11b protein, mouse
Tnfsf10 protein, mouse
Matrix Metalloproteinase 9
Mmp9 protein, mouse
Calcium Chloride

Grants and funding

This work was supported by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology in Japan.