"Osteoprotegerin prevents development of abdominal aortic aneurysm"
Dr. Bumdelger Batmunkh
Assistance professor, Hiroshima University
Abstract:
Introduction: Abdominal aortic aneurysm (AAA) is a dilatation of aorta more than 3cm in diameter, due to loss of elasticity and degenerative weakening of its wall. It is found in 5% of men over 65 years old. When aortic diameter reaches 5cm it is accompanied by a risk of rupture and subsequent high mortality. At the time only surgical treatment is available, however it is not a perfect treatment. Discovery of an effective medicine which prevents aneurysm expansion is highly required. Detailed understanding of molecular pathogenesis of the disease is necessary for development of the medicine. Recently, Osteoprotegerin (OPG), known as a main regulator of bone metabolism, has been also found to have anti-calcification activity and anti-atherosclerotic effects on aorta.
Purpose: We hypothesized a possible involvement of OPG in the prevention of AAA through inhibition of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
Methods: AAA was generated via peri-aortic application of CaCl2 in the OPG-Knockout (Opg-KO) mice. Histological and immunohistochemical analyses of mice aorta were performed. Mouse aortic smooth muscle cells (SMCs) culture system was used to examine the effect of OPG on TRAIL-induced signaling. Activation of c-Jun N-terminal kinase (JNK) and up-regulation of matrix metalloproteinase (MMP9) were detected by Western blotting and Real-time PCR, respectively. Effect of OPG on SMC and Macrophage migration was also tested by Boyden chamber assay.
Results: In Opg-KO mice, both aortic internal and external diameters were significantly increased, accompanied with destruction of medial elastic fibers, as compared to wild-type mice. This result suggests that the absence of OPG gene enhanced the formation of AAA. In Wild-type mice, expression of OPG in the aortic tissue was up-regulated in response to AAA induction, probably due to self-defensive compensatory reaction to inflammation. TRAIL expression was increased in aortic wall in the Opg-KO mice. In addition, MMP9 and activated JNK were co-localized with the TRAIL expression. In SMC culture system, TRAIL-induced JNK activation and MMP9 up-regulation were found, which was inhibited by OPG. OPG also inhibited the chemo-attractive effect of TRAIL on SMCs and macrophages.
Conclusion: Our results suggest that OPG may have a preventive role on the development of AAA through its antagonistic effect on TRAIL.
Brief Introduction:
Professional experience
2019 – present Hiroshima University, Graduate School of Biomedical & Health Sciences , Assistant Professor
2013 – 2019 Hiroshima University, Institute of Biomedical & Health Sciences, Assistant Professor
2006 – 2009 National Institute of Medicine named by T. Shagdarsuren, Central Scientific Research Laboratory, Researcher
2005 – 2009 Monolab LLC, Clinical laboratory Scientist (Application Specialist)
Educational Backgrounds
2009 – 2013 Hiroshima University, Graduate School of Biomedical and Health Sciences, Department of Biomedical Sciences, PhD degree
2005 – 2007 Health Sciences University of Mongolia, Postgraduate Institute, Clinical Laboratory Residency Training Program
1998 – 2005 Health Sciences University of Mongolia, School of Medicine, Bachelor’s degree in medical science
Research work
Current status of hematology and immunology in Mongolia, Journal of Science (Abstracts of presentations for 45th anniversary of the establishment of National Institute of Mongolia named by T. Shagdarsuren, 2006)
Induction of Timp1 in smooth muscle cells during development of abdominal aortic aneurysms, Hiroshima Journal of Medical Sciences, 62(3), 63-67, Sep 2013
Osteoprotegerin prevents development of abdominal aortic aneurysms, PLOS ONE, 11(1), JAN 19 2016
EPA prevents the development of abdominal aortic aneurysms through Gpr-120/Ffar-4, PLOS ONE, 11(10), OCT 20, 2016
The SGLT2 inhibitor luseogliflozin rapidly normalizes aortic mRNA levels of inflammation-related but not lipid-metabolism-related genes and suppresses atherosclerosis in diabetic ApoE KO Mice, International Journal of Molecular Sciences, 18(8), Aug 2017