The role of immunoglobulins and Syk in pathogenesis of abdominal aortic aneurysm

• Project/Area Number: 15K19928
• 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): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 大動脈瘤 / B細胞 / 免疫グロブリン / Syk / 慢性炎症 / 腹部大動脈瘤 / 炎症

Outline of Final Research Achievements

In this project, we examined the role of immunoglobulins (Ig) and Syk in pathogenesis of abdominal aortic aneurysm (AAA) using human AAA tissue culture and mouse AAA. We found that B cell-deficient mice (mu-MT) developed smaller AAA than wild type (WT) mice. Administration of mouse Ig to mu-MT resulted in larger AAA with higher activation of inflammatory signaling molecules including Syk and higher expression of MMP-9. In human AAA tissue culture, administration of human Ig resulted in the increase in secretions of IL-6 and MMP-9. In mouse AAA, administration of fostamatinib, a specific Syk inhibitor, effectively suppressed activations of Syk and JNK and deposition of Ig in AAA tissue. These findings indicate that B cells, Ig and Syk constitute an essential part of inflammatory pathway in AAA pathogenesis. Future research should be directed to examine the clinical application of these findings for novel diagnostic and therapeutic strategies.

Research Products

• [Presentation] Importance of Immunoglobulin-dependent Tissue Destruction in Abdominal Aortic Aneurysm. (2017)
  • Author(s): 4.A. Furusho, H. Aoki, M. Nishihara, S. Ohno, S. Hirakata, N. Nishida, S. Ito, M. Hayashi, Y. Fukumoto
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-18
  • Int'l Joint Research
• [Presentation] B cells promote abdominal aortic aneurysm and aortic dissection through proinflammatory function of immunoglobulins. (2016)
  • Author(s): 4.A. Furusho, H. Aoki, M. Nishihara, S. Ohno, S. Hirakata, N. Nishida, S. Ito, M. Hayashi, H. Akashi, H. Tanaka, Y. Fukumoto
  • Organizer: ESC Congress Rome 2016
  • Place of Presentation: Rome, Italy
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] B cells promote abdominal aortic aneurysm and aortic dissection through proinflammatory function of immunoglobulins (2016)
  • Author(s): Aya Furusho
  • Organizer: 第80回日本循環器学会学術集会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-20
• [Book] Mouse Model of Abdominal Aortic Aneurysm Induced by CaCl2. in Mouse Models of Vascular Diseases. ed. Masataka Sata (2016)
  • Author(s): 1.Hiroki Aoki, Satoko Ohno, Aya Furusho, Michihide Nishihara, Norifumi Nishida, Saki Hirakata, Koichi Yoshimura
  • Total Pages: 296
  • Publisher: Springer Japan (Tokyo)