The Effects of Biological Stress Responses on the Development of Atherosclerosis.

• Project/Area Number: 24591107
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Iwate Medical University (2013-2014); Tohoku University (2012)
• Principal Investigator: ISHIGAKI Yasushi 岩手医科大学, 医学部, 教授 (50375002)
• Co-Investigator(Kenkyū-buntansha): GAO Junhong 東北大学, 大学院医学系研究科, 助教 (70455781) ; SHOUJIROU Sawada 東北大学, 大学院医学系研究科, 助教 (60509420)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 動脈硬化 / 小胞体ストレス / 酸化ストレス

Outline of Final Research Achievements

The interactions among biological pathways, such as responses to inflammation, oxidative stress and endoplasmic reticulum (ER) stress are thought to be important for the development of atherosclerosis. Wolfram Syndrome (WFS) 1, which regulates ER stress response genes, is expressed in vascular endothelial cells, smooth muscle cells and macrophages. Cuff injury-induced vascular remodeling and hypercholesterolemia-induced aortic plaque formation were markedly advanced in WFS1-/- mice with exacerbated aortic expressions of inflammatory factors and oxidative stress markers. The results of studies in vitro revealed that WFS1 directly modulate inflammatory and oxidative stress response in vascular cells as well as macrophage. Thus, WFS1 may play important roles in suppressing potentially pathological biological stress responses, resulting in prevention of atherosclerosis.

Research Products

• [Journal Article] Response to the dipeptidyl peptidase-4 inhibitors in Japanese patients with type 2 diabetes might be associated with a diplotype of two single nucleotide polymorphisms on the interleukin-6 promoter region under a certain level of physical activity. (2015)
  • Author(s): 4.Matsui M, Takahashi Y, Takebe N, Takahashi K, Nagasawa K, Honma H, Oda T, Ono M, Nakagawa R, Sasai T, Togashi H, Hangai M, Kajiwara T, Taneichi H, Ishigaki Y, Satoh J.
  • Journal Title: J Diabetes Invest. Volume: 6 Issue: 2 Pages: 173-181
  • DOI: 10.1111/jdi.12260
  • Peer Reviewed / Open Access
• [Journal Article] Positive association of free triiodothyronine with pancreatic β-cell function in people with prediabetes. (2015)
  • Author(s): 2.Oda T, Taneichi H, Takahashi K, Togashi H, Hangai M, Nakagawa R, Ono M, Matsui M, Sasai T, Nagasawa K, Honma H, Kajiwara T, Takahashi Y, Takebe N, Ishigaki Y, Satoh J.
  • Journal Title: Diabet Med. Volume: 印刷中 Issue: 2 Pages: 213-219
  • DOI: 10.1111/dme.12589
  • Peer Reviewed
• [Journal Article] Impacts of the Great East Japan Earthquake on diabetic patients. (2015)
  • Author(s): anaka M, Imai J, Satoh M, Hashimoto T, Izumi T, Sawada S, Uno K, Hasegawa Y, Kaneko K, Yamada T, Ishigaki Y, Imai Y and Katagiri H.
  • Journal Title: J Diabetes Invest. Volume: 印刷中 Issue: 5 Pages: 1-10
  • DOI: 10.1111/jdi.12336
  • Peer Reviewed / Open Access
• [Journal Article] Elevation of HDL-C in Response to Statin Treatment is Involved in the Regression of Carotid Atherosclerosis. (2014)
  • Author(s): Ishigaki Y, Kono S, Katagiri H, Oka Y, Oikawa S; NTTP investigators.
  • Journal Title: J Atheroscler Thromb. Volume: 21 Pages: 1055-1065
  • NAID: 130004700288
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Glycemic control in diabetic patients with impaired endogenous insulin secretory capacity is vulnerable after a natural disaster: study of Great East Japan Earthquake (2014)
  • Author(s): Tanaka M, Imai J, Satoh M, Hashimoto T, Izumi T, Sawada S, Uno K, Hasegawa Y, Kaneko K, Yamada T, Ishigaki Y, Imai Y, Katagiri H
  • Journal Title: Diabetes Care Volume: 37(10) Issue: 10 Pages: e212-e213
  • DOI: 10.2337/dc14-1479
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Insulin-Mimicking Bioactivities of Acylated Inositol Glycans in Several Mouse Models of Diabetes with or without Obesity. (2014)
  • Author(s): 5.Suzuki S, Suzuki C, Hinokio Y, Ishigaki Y, Katagiri H, Kanzaki M, Azev VN, Chakraborty N, d'Alarcao M.
  • Journal Title: PLoS One. Volume: 9 Issue: 6 Pages: e100466-e100466
  • DOI: 10.1371/journal.pone.0100466
  • Peer Reviewed / Open Access
• [Journal Article] Simultaneous copy number losses within multiple subtelomeric regions in early-onset type 2 diabetes mellitus (2014)
  • Author(s): Kodama S, Yamada T, Imai J, Sawada S, Takahashi K, Tsukita S, Kaneko K, Uno K, Ishigaki Y, Oka Y, Katagiri H
  • Journal Title: PLoS One Volume: 9(4) Issue: 4 Pages: e88602-e88602
  • DOI: 10.1371/journal.pone.0088602
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Bach1 deficiency protects pancreatic β-cells from oxidative stress injury. (2013)
  • Author(s): Kondo K, Ishigaki Y, Gao J, Yamada T, Imai J, Sawada S, Muto A, Oka Y, Igarashi K, Katagiri H.
  • Journal Title: Am J Physiol Endocrinol Metab. Volume: 305(5) Issue: 5 Pages: E641-E648
  • DOI: 10.1152/ajpendo.00120.2013
  • Peer Reviewed
• [Journal Article] Clinical Experiences in the Treatment of Pancreatic Arteriovenous Malformation by Total Pancreatectomy With Islet Autotransplantation. (2013)
  • Author(s): Sakata N, Goto M, Motoi F, Hayashi H, Nakagawa K, Mizuma M, Yamaya H, Hasegawa Y, Yamaguchi S, Sawada S, Ottomo S, Okada T, Fukase K, Yoshida H, Ito T, Hirota M, Ishigaki Y, Sekiguchi S, Rikiyama T, Katayose Y, Fujimori K, Egawa S, Shimosegawa T, Katagiri H, Satomi S, Unno M
  • Journal Title: Transplantation Volume: 96(5) Issue: 5 Pages: e38-e40
  • DOI: 10.1097/tp.0b013e3182a01333
  • Peer Reviewed
• [Journal Article] Cognitive dysfunction associated with anti-glutamic acid decarboxylase autoimmunity: a case-control study. (2013)
  • Author(s): Takagi M, Ishigaki Y, Uno K, Sawada S, Imai J, Kaneko K, Hasegawa Y, Yamada T, Tokita A, Iseki K, Kanno S, Nishio Y, Katagiri H and Mori E
  • Journal Title: BMC Neurol Volume: 13 Issue: 1 Pages: 76-76
  • DOI: 10.1186/1471-2377-13-76
  • Peer Reviewed
• [Presentation] 脳卒中予防のための脂質管理 (2015)
  • Author(s): 石垣 泰
  • Organizer: 第40回日本脳卒中学会
  • Place of Presentation: 広島
  • Year and Date: 2015-03-28
  • Invited
• [Presentation] 大血管障害発症予防を目指した糖尿病診療 (2014)
  • Author(s): 石垣 泰
  • Organizer: 第28回日本臨床内科医会
  • Place of Presentation: 盛岡
  • Year and Date: 2014-10-12
  • Invited
• [Presentation] さまざまな臓器の糖代謝調節における小胞体ストレスの役割 (2014)
  • Author(s): 石垣 泰
  • Organizer: 第29回日本糖尿病合併症学会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-04
  • Invited
• [Presentation] 糖尿病内科医からみたMetabolic Surgeryの有用性 (2014)
  • Author(s): 石垣 泰
  • Organizer: 第27回日本内視鏡外科学会
  • Place of Presentation: 盛岡
  • Year and Date: 2014-10-02
  • Invited
• [Presentation] 術前における減量の重要性 (2014)
  • Author(s): 石垣 泰
  • Organizer: 第32回日本肥満症治療学会
  • Place of Presentation: 大津
  • Year and Date: 2014-07-04
  • Invited
• [Presentation] 肥満患者と健常者における食物刺激に対する渇望反応の差異 (2013)
  • Author(s): 村椿智彦
  • Organizer: 第34回日本肥満学会
  • Place of Presentation: 東京
• [Presentation] 1型と2型糖尿病患者の頸動脈血管弾性特性の比較検討 (2013)
  • Author(s): 澤田正二郎
  • Organizer: 第45回日本動脈硬化学会学術集会
  • Place of Presentation: 東京
• [Presentation] 肝GKによるBAT熱産生低下が個体のエネルギー代謝に及ぼす効果は飼育温度に影響される (2013)
  • Author(s): 突田壮平
  • Organizer: 第34回日本肥満学会
  • Place of Presentation: 東京