The role of B cells in pathogenesis of abdominal aortic aneurysm

• Project/Area Number: 25861237
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular surgery
• Research Institution: Kurume University
• Principal Investigator: FURUSHO AYA 久留米大学, 医学部, 助教 (80597427)
• 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: 大動脈瘤 / 慢性炎症 / B細胞 / 免疫グロブリン / 炎症

Outline of Final Research Achievements

In this project, we examined the role of B cells in pathogenesis of abdominal aortic aneurysm (AAA) using human AAA tissue culture and mouse model of AAA. We found that B cell-deficient mice (mu-MT) developed smaller AAA than wild type (WT) mice, which was associated with reduced activities of JNK and MMP-9. Administration of mouse immunoglobulins to mu-MT resulted in larger AAA with higher expression of MMP-9, indicating that the presence of immunoglobulins was required for the full formation of AAA. Furthermore, treatment of human AAA tissue in culture with human immunoglobulins significantly increased secretions of MMP-9 and IL-6, consistent with the findings in mouse AAA model. These findings indicate that B cells promote AAA through the proinflammatory effect of immunoglobulins. Elucidation of the role of B cells and immunoglobulins will provide a new insight into the AAA pathogenesis that is essential for the development of novel diagnostic and therapeutic strategies.

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] B cells Promote the Development of Abdominal Aortic Aneurysm through a proimflammatory response (2014)
  • Author(s): Aya Furusho, Hiroki Aoki, Michihide Nishihara, Satoko Ohno, Saki Hirakata, Norifumi Nishida, Sohei Ito, Makiko Hayashi, Yoshihiro Fukumoto
  • Organizer: 第３１回国際心臓研究学会
  • Place of Presentation: ウインクあいち
  • Year and Date: 2014-11-28 – 2014-11-29
• [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: European Society Of Cardiology 2014
  • Place of Presentation: Barcelona
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] B Cells and Immunoglobulin Promotes Development of Abdominal Aortic Aneurysm (2014)
  • 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: 大阪国際会議場
  • Year and Date: 2014-04-24 – 2014-04-26
• [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: Kyoto Miyakomesse
• [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: Tokyo International Forum
• [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: Kyoto Miyakomesse
• [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: Tokyo International Forum
• [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,Texas
• [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,Texas