The development of innovative drug therapy in aortic dissection

• Project/Area Number: 25861236
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular surgery
• Research Institution: Kurume University
• Principal Investigator: NISHIDA Norifumi 久留米大学, 医学部, 助教 (50624508)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 大動脈解離 / ピオグリタゾン / 塩分過剰 / IL-17

Outline of Final Research Achievements

In this project, we investigated whether pioglitazone suppresses aortic dissection. Unexpectedly, pioglitazone worsened the aortic dissection in mice. We hypothesized that sodium retention by pioglitazone might be the underlying mechanism. In fact, excessive sodium intake worsened aortic dissection through IL-17 pathway. Transcriptome analysis of aortae before the onset of aortic dissection showed strong induction of proinflammatory genes and suppression of extracellular matrix genes. Deletion of IL-17 gene resulted in the augmented expression of extracellular matrix genes and enhanced collagen deposition. From these results, we concluded that IL-17 suppresses the extracellular matrix synthesis, which in turn worsens aortic dissection. We will continue to explore the mechanism of aortic dissection, focussing on the roles of IL-17 and extracellular matrix.

Research Products

• [Journal Article] Tenascin C protects aorta from acute dissection in mice. (2014)
  • Author(s): Kimura, T., K. Shiraishi, A. Furusho, S. Ito, S. Hirakata, N. Nishida, K. Yoshimura, K. Imanaka-Yoshida, T. Yoshida, Y. Ikeda, T. Miyamoto, T. Ueno, K. Hamano, M. Hiroe, K. Aonuma, M. Matsuzaki, T. Imaizumi, and H. Aoki.
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 4051-4051
  • DOI: 10.1038/srep04051
  • Peer Reviewed / Open Access
• [Presentation] Excessive sodium intake worsens aortic dissection via IL-17 Pathway (2015)
  • Author(s): Norifumi Nishida, Hiroki Aoki, Satoko Ohno, Michihide Nishihara, Aya Furusho, Saki Hirakata, Makiko Hayashi, Sohei Ito, Hideo Yasukawa, Yoshihiro Fukumoto
  • Organizer: Europian Society of Cardiology Congress 2015
  • Place of Presentation: Excel London
  • Year and Date: 2015-08-29 – 2015-09-02
• [Presentation] Excessive Sodium Intake Exacerbates Aortic Dissection through IL-17 Pathway (2015)
  • Author(s): 西田憲史、青木浩樹、大野聡子、西原通秀、古荘文、平方佐季、林真貴子、伊東壮平、安川秀雄、福本義弘
  • Organizer: 第79回日本循環器学会学術総会
  • Place of Presentation: グランフロント大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] Molecular Pathogenesis of Aortic Dissection: Macrophage-mediated Changes in Vascular Smooth Muscle-specific Gene Expression (2015)
  • Author(s): Satoko Ohno, Hiroki Aoki, Michihide Nishihara, Aya Furusho, Saki Hirakata, Norifumi Nishida, Sohei Ito, Makiko Hayashi, Yoshihiro Fukumoto
  • Organizer: 第79回日本循環器学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] B Cells and Immunoglobulin Promotes Development of Abdominal Aortic Aneurysm (2015)
  • Author(s): Aya Furusho, Hiroki Aoki, Michihide Nishihara, Satoko Ohno, Saki Hirakata, Norifumi Nishida, Sohei Ito, Makiko Hayashi, Yoshihiro Fukumoto
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] Protective Role of STAT3 in Vascular Smooth Muscle Cells During the Development of Aortic Dissection (2015)
  • Author(s): Saki Hirakata, Hiroki Aoki, Michihide Nishihara, Satoko Ohno, Aya Furusho, Norifumi Nishida, Sohei Ito, Makiko Hayashi, Yoshihiro Fukumoto
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] 塩分過剰摂取はIL-17経路を介して大動脈解離を増悪させる (2015)
  • Author(s): 西田憲史、青木浩樹、大野聡子、西原通秀、古荘文、平方佐季、林真貴子、伊東壮平、安川秀雄、福本義弘
  • Organizer: 第44回日本心脈管作動物質学会
  • Place of Presentation: 高知センタービル
  • Year and Date: 2015-02-06 – 2015-02-07
• [Presentation] Excessive Sodium Intake Exacerbates Acute Aortic Dissection through Proinflammatory IL-17 Pathway (2014)
  • Author(s): Norifumi Nishida, Hiroki Aoki, Satoko Ohno, Michihide Nishihara, Aya Furusho, Saki Hirakata, Makiko Hayashi, Sohei Ito, Hideo Yasukawa, Yoshihiro Fukumoto
  • Organizer: 第31回国際心臓研究学会日本支部会
  • Place of Presentation: ウインクあいち
  • Year and Date: 2014-11-28 – 2014-11-29
• [Presentation] Involvement of Macrophage IL-6 Signaling in Aortic Dissection (2014)
  • Author(s): Satoko Ohno, Hiroki Aoki, Aya Furusho, Saki Hirakata, Norifumi Nishida, Sohei Ito, Makiko Hayashi, Yoshihiro Fukumoto
  • Organizer: 第31回国際心臓研究学会日本支部会
  • Place of Presentation: ウインクあいち
  • Year and Date: 2014-11-28 – 2014-11-29
• [Presentation] Protective role of STAT3 in vascular smooth muscle cells during the development of acute aortic dissection (2014)
  • Author(s): Saki Hirakata, Hiroki Aoki, Michihide Nishihara, Satoko Ohno, Aya Furusho, Norifumi Nishida, Sohei Ito, Makiko Hayashi, Yoshihiro Fukumoto
  • Organizer: 第31回国際心臓研究学会日本支部会
  • Place of Presentation: ウインクあいち
  • Year and Date: 2014-11-28 – 2014-11-29
• [Presentation] A Common Gene Network Governs The Cellular Phenotypes in Acute Aortic Dissection (2014)
  • Author(s): Satoko Ohno, Hiroki Aoki, Michihide Nishihara, Aya Furusho, Saki Hirakata, Norifumi Nishida, Sohei Ito, Hideo Yasukawa, Yoshihiro Fukumoto
  • Organizer: American Heart Association Scientific sessions 2014
  • Place of Presentation: Chicago
  • Year and Date: 2014-11-16 – 2014-11-20
• [Presentation] Protective role of STAT3 in vascular smooth muscle cells during the development of acute aortic dissection (2014)
  • Author(s): Saki Hirakata, Hiroki Aoki, Michihide Nishihara, Satoko Ohno, Aya Furusho, Norifumi Nishida, Sohei Ito, Yoshihiro Fukumoto
  • Organizer: American Heart Association Scientific sessions 2014
  • Place of Presentation: Chicago
  • Year and Date: 2014-11-16 – 2014-11-20
• [Presentation] Molecular determinant of the development of acute aortic dissection (2014)
  • Author(s): Satoko Ohno, Hiroki Aoki, Michihide Nishihara, Aya Furusho, Saki Hirakata, Norifumi Nishida, Sohei Ito, Yoshihiro Fukumoto
  • Organizer: Europian Society of Cardiology Congress 2014
  • Place of Presentation: Barcelona
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] The Role of B Cells in Pathogenesis of Abdominal Aortic Aneurysm (2014)
  • Author(s): Aya Furusho, Hiroki Aoki, Michihide Nishihara, Satoko Ohno, Saki Hirakata, Norifumi Nishida, Sohei Ito, Yoshihiro Fukumoto
  • Organizer: Europian Society of Cardiology Congress 2014
  • Place of Presentation: Barcelona
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] Involvement of B cells in Pathogenesis of Abdominal Aortic Aneurysm (2014)
  • Author(s): Aya Furusho, Hiroki Aoki, Michihide Nishihara, Satoko Ohno, Saki Hirakata, Norifumi Nishida, Sohei Ito, Yoshihiro Fukumoto
  • Organizer: International Vascular Biology Meeting 2014
  • Place of Presentation: 京都
• [Presentation] Involvement of Macrophage Cytokine Signaling in Acute Aortic Dissection (2014)
  • Author(s): Satoko Ohno, Hiroki Aoki , Michihide Nishihara , Aya Furusho , Saki Hirakata , Norifumi Nishida , Souhei Itou , Yoshihiro Fukumoto
  • Organizer: International Vascular Biology Meeting 2014
  • Place of Presentation: 京都
• [Presentation] Involvement of B cells in Pathogenesis of Abdominal Aortic Aneurysm (2014)
  • Author(s): Aya Furusho, Hiroki Aoki, Michihide Nishihara, Satoko Ohno, Saki Hirakata, Norifumi Nishida, Sohei Ito, Yoshihiro Fukumoto
  • Organizer: The 78th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 東京
• [Presentation] Macrophage Cytokine Signaling Dtermines the Development of Acute Aortic Dissection (2014)
  • Author(s): Satoko Ohno, Hiroki Aoki, Michihide Nishihara, Aya Furusho, Saki Hirakata, Norifumi Nishida, Souhei Ito, Hideo Yasukawa, Tsutomu Imaizumi, Yoshihiro Fukumoto
  • Organizer: The 78th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 東京
• [Presentation] Deciphering the Sequential Molecular Events During Onset of Acute Aortic Dissection (2013)
  • Author(s): Satoko Ohno, Hiroki Aoki, Michihide Nishihara, Aya Furusho, Saki Hirakata, Norifumi Nishida, Souhei Itou, Tsutomu Imaizumi
  • Organizer: American Heart Association Scientific sessions 2013
  • Place of Presentation: Dallas
• [Presentation] Involvement of IL-6 in Pathogenesis of Abdominal Aortic Aneurysm (2013)
  • Author(s): Michihide Nishihara, Hiroki Aoki, Satoko Ohno, Aya Furusho, Saki Hirakata, Norifumi Nishida, Sohei Ito, Tsutomu Imaizumi
  • Organizer: American Heart Association Scientific sessions 2013
  • Place of Presentation: Dallas