The molecular mechanism of radiation-induced acceleration of atherosclerosis

• Project/Area Number: 26461852
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Fukushima Medical University (2016); Hiroshima University (2014-2015)
• Principal Investigator: Takafumi Ishida 福島県立医科大学, 医学部, 教授 (40346482)
• Co-Investigator(Kenkyū-buntansha): 石田 万里 広島大学, 医歯薬保健学研究院(医), 講師 (30359898)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: DNA損傷 / 動脈硬化 / 放射線被ばく / 放射線 / ゲノム障害

Outline of Final Research Achievements

It has been well recognized that radiotherapy increases the risk of atherosclerotic cardiovascular disease. The object of this study was to clarify the mechanism of radiation-induced acceleration of atherosclerosis. Thoracic aorta of apoE-deficient (apoE-KO) mice were irradiated with the dose of 10Gy and kept on a normal chow diet for 8 weeks. The plaque area was significantly increased in aortic roots of irradiated apoE-KO mice compared with control mice. Infiltration of inflammatory cells and hemorrhage was observed in the plaque. Additionally, immunohistochemical study revealed that gamma-H2AX and phospho-ATM staining were increased in the plaque of irradiated apoE-KO mice. These results suggest that accumulation of DNA damage and activation of DNA damage response is involved in the mechanism of radiation-induced acceleration of atherosclerosis.

Research Products

• [Journal Article] DNA damage in lymphocytes induced by cardiac CT and comparison with physical exposure parameters. (2017)
  • Author(s): Fukumoto W, Ishida M, Sakai C, Tashiro S, Ishida T, Nakano Y, Tatsugami F, Awai K.
  • Journal Title: European Radiology Volume: 27 Issue: 4 Pages: 1660-1666
  • DOI: 10.1007/s00330-016-4519-8
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] EPA Prevents the Development of Abdominal Aortic Aneurysms through Gpr-120/Ffar-4. (2016)
  • Author(s): Kamata R, Bumdelger B, Kokubo H, Fujii M, Yoshimura K, Ishida T, Ishida M, Yoshizumi M.
  • Journal Title: PLoS One Volume: 11 Issue: 10 Pages: 0165132-0165146
  • DOI: 10.1371/journal.pone.0165132
  • Peer Reviewed / Open Access
• [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
  • Peer Reviewed / Open Access
• [Journal Article] Smoking cessation reverses DNA double-strand breaks in human mononuclear cells. (2014)
  • Author(s): Ishida M
  • Journal Title: PLoS One Volume: 9 Issue: 8 Pages: 1-9
  • DOI: 10.1371/journal.pone.0103993
  • Peer Reviewed / Open Access
• [Journal Article] Reorganization of Damaged Chromatin by the Exchange of Histone Variant H2A.Z-2. (2014)
  • Author(s): Nishibuchi I
  • Journal Title: Int J Radiat Oncol Biol Phys. Volume: 89 Issue: 4 Pages: 736-744
  • DOI: 10.1016/j.ijrobp.2014.03.031
  • Peer Reviewed / Open Access
• [Presentation] XRCC3 polymorphism is associated with hypertension-induced left ventricular Hypertrophy (2017)
  • Author(s): Chiemi Sakai, Andi Ariyandy, Mari Ishida, Masao Yoshizumi, Takafumi Ishida
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] 放射線診断検査によるDNA損傷の検討 (2016)
  • Author(s): 石田万里、坂井千恵美、福本航、粟井和夫、吉栖正生、石田隆史
  • Organizer: 第57回日本脈管学会総会
  • Place of Presentation: 奈良
  • Year and Date: 2016-10-13
• [Presentation] n-3系多価不飽和脂肪酸は血管内皮細胞のDNA損傷を軽減する (2016)
  • Author(s): 坂井千恵美、石田万里、上田瞳、吉栖正生、石田隆史
  • Organizer: 第39回日本高血圧学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-30
• [Presentation] ゲノム修復関連蛋白XRCC3の遺伝子多型と心肥大の関連． (2015)
  • Author(s): 坂井千恵美、石田万里、アリヤンディ アンディ、日下美穂、平沼浩司、吉栖正生、石田隆史
  • Organizer: 第38回日本高血圧学会総会
  • Place of Presentation: 松山市
  • Year and Date: 2015-10-09
• [Presentation] Fish oils, eicosapentaenoic acid and docosahexaenoic acid, attenuate oxidative stress-induced DNA damage in vascular endothelial cells. (2015)
  • Author(s): Chiemi Sakai, Mari Ishida, Yasuki Kihara, Masao Yoshizumi, Takafumi Ishida
  • Organizer: European Society of Cardiology Congress 2015
  • Place of Presentation: London, UK
  • Year and Date: 2015-08-29
  • Int'l Joint Research