Elucidation of the mechanism of development of different types of aneurysm

• Project/Area Number: 25461142
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Juntendo University (2014-2015); National Defense Medical College (2013)
• Principal Investigator: Isoda Kikuo 順天堂大学, 医学部, 准教授 (00532475)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 動脈瘤 / 炎症 / サイトカイン / 骨髄 / DPP-4阻害 / アンジオテンシンII / DPP-４阻害薬 / 抗炎症性サイトカイン / 炎症細胞

Outline of Final Research Achievements

We detected that the IL-1Ra present in both bone marrow (BM)-derived cells and non-BM cells helps to suppress arterial inflammation and promote re-endothelialization, thus resulting in decreased neointimal formation and development of aneurysm. These novel findings shed new light on the mechanisms underlying the development of aneurysm. We also revealed that a dipeptidyl‐peptidase‐4 inhibitor appeared to suppress neointimal formation by inhibiting inflammation, independently of its effects on glucose or cholesterol metabolism in mice. We have published these articles.

Research Products

• [Journal Article] Lack of IkBNS accelerates atheroclerosis in LDL receptor-deficient mice via increased interleukin-6 production (2016)
  • Author(s): Akita K, Isoda K, Okabayasi Y, Shimada K, Daida H
  • Journal Title: International Journal of Cardiology Volume: 211 Pages: 61-63
  • DOI: 10.1016/j.ijcard.2016.02.142
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Dipeptidyl-peptidase-4 inhibitor, alogliptin, attenuates arterial inflammation and neointimal formation after injury in low-density lipoprotein (LDL) receptor-deficient mice. (2015)
  • Author(s): Akita K, Isoda K, Shimada K, Daida H
  • Journal Title: J Am Heart Assoc Volume: 4 Issue: 3
  • DOI: 10.1161/jaha.114.001469
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Interleukin-1 Receptor Antagonist Originating from Bone Marrowderived Cells and Non-bone Marrow-derived Cells Helps to Suppress Arterial Inflammation and Reduce Neointimal Formation after Injury (2014)
  • Author(s): Isoda K, Akita K, Isobe S, Niida T, Adachi T, Iwakura Y, Daida H
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 21 Issue: 11 Pages: 1208-1218
  • DOI: 10.5551/jat.25668
  • NAID: 130004690941
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Interleukin-1receptor antagonist contributes to the suppression of both angiotensin II-induced hypertention and organ damage. (2015)
  • Author(s): Koji Akita, Kikuo Isoda, Hiroyuki Daida
  • Organizer: ESC congress 2015
  • Place of Presentation: London
  • Year and Date: 2015-08-29
  • Int'l Joint Research
• [Presentation] インターロイキン1受容体アンタゴニストはアンジオテンシンII投与によって誘導された動脈の炎症及び瘤形成を抑制する (2015)
  • Author(s): 秋田耕嗣、磯田菊生、代田浩之
  • Organizer: 第47回日本動脈硬化学会
  • Place of Presentation: 仙台
  • Year and Date: 2015-07-09
• [Presentation] The Role of Interleukin-1 Receptor Antagonist in the Suppresion of Aortic Inflammation and Aneurysm after Angiotensin II Infusion (2015)
  • Author(s): Koji Akita, Kikuo Isoda, Hiroyuki Daida
  • Organizer: The 79th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24
• [Presentation] Deficiency of Interleukin-1 Receptor Antagonist Promotes Angiotensin II-induced Aortic Inflammation and Aneurysm (2014)
  • Author(s): Koji Akita, Kikuo Isoda, Hiroyuki Daida
  • Organizer: AHA Scientific Session 2014
  • Place of Presentation: Chicago
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] The Effect of Interleukin-1 Receptor Antagonist from both Bone Marrow-Derived Cells and Non-bone Marrow Cells in Arterial Inflammation and Neointimal Formation after Injury (2014)
  • Author(s): Kikuo Isoda, Koji Akita, Manabu Kitagaki, Sarasa Isobe, Tomiharu Niida, Takeshi Adachi
  • Organizer: The 78th Annual Scientific Meeting of the Japanese Atherosclerosis Society
  • Place of Presentation: 東京、京王プラザホテル
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] Interleukin-1 receptor antagonist from both bone marrow-derived cells and non-bone marrow cells helps suppress arterial inflammation after injury (2014)
  • Author(s): 磯田菊生
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京国際フォーラム（東京）
• [Presentation] The role of interleukin-1 receptor antagonist in angiotensin II-induced hypertension and renal damages (2014)
  • Author(s): 磯部更紗、磯田菊生
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京国際フォーラム（東京）
• [Presentation] Interleukin-1 receptor antagonist in bone marrow-derived cells helps suppress arterial inflammation and reduces neointimal formation after injury (2013)
  • Author(s): 磯田菊生
  • Organizer: 第45回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 京王プラザホテル（新宿）
• [Presentation] Alogliptin, a dipeptidyl peptidase-4 inhibitor, suppresses arterial inflammation and neointimal formation after injury (2013)
  • Author(s): 秋田耕嗣、磯田菊生
  • Organizer: 第45回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 京王プラザホテル（新宿）
• [Presentation] Interleukin-1 receptor antagonist deficiency promotes angiotensin II-induced hypertension and renal damage (2013)
  • Author(s): 磯部更紗、磯田菊生
  • Organizer: American Heart Association Scientific Sessions 2013
  • Place of Presentation: Dallas Convention Center (Dallas, USA)