Molecular mechanism for arteriosclerosis and aortic aneurysm

• Project/Area Number: 25461130
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Hiroshima University
• Principal Investigator: Yoshizumi Masao 広島大学, 医歯薬保健学研究科, 教授 (20282626)
• Co-Investigator(Kenkyū-buntansha): Kokubo Hiroki 広島大学, 大学院医歯薬保健学研究院(医), 講師 (10270480)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 大動脈瘤 / Osteoprotegerin / オステオプロテジェリン / Trail / エイコサペンタエン酸 / Jun Kinase / 動脈硬化

Outline of Final Research Achievements

We have demonstrated the possible involvement of Osteoprotegerin (OPG) in the prevention of AAAs through inhibition of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). After the induction of AAA by CaCl2 treatment, diameters of aorta 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 assay. In smooth muscle cells (SMCs) culture system, both the TRAIL-induced expression of matrix metalloproteinase-9 and the chemoattractive effect of TRAIL on SMCs were inhibited by OPG. These data suggest that Opg may play a protective role in the development of AAA through its antagonistic effect on Trail.

Research Products

• [Journal Article] Osteoprotegerin Prevents Development of Abdominal Aortic Aneurysms. (2016)
  • Author(s): Bumdelger B, Kokubo H, Kamata R, Fujii M, Yoshimura K, Aoki H, Orita Y, Ishida T, Ohtaki M, Nagao M, Ishida M, Yoshizumi M.
  • Journal Title: PLoS One Volume: 11 Issue: 1 Pages: 147088-147107
  • DOI: 10.1371/journal.pone.0147088
  • Peer Reviewed / Open Access
• [Journal Article] Induction of Timp1 in smooth muscle cells during development of abdominal aortic aneurysms. (2013)
  • Author(s): Bumdelger B, Kokubo H, Kamata R, Fujii M, Ishida M, Ishida T, Yoshizumi M.
  • Journal Title: Hiroshima J Med Sci. Volume: 62 Pages: 63-67
  • NAID: 120005396042
  • Peer Reviewed
• [Presentation] Induction of Timp1 in smooth muscle cells during development of abdominal aortic aneurysms.
  • Author(s): Bumdelger B, Kokubo H, Kamata R, Fujii M, Ishida M, Ishida T, Yoshizumi M.
  • Organizer: International Vascular Biology Meeting 2014
  • Place of Presentation: Kyoto