Role of JCAD in the pathogenesis of plaque destabilization

• Project/Area Number: 16K09515
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kobe University
• Principal Investigator: Kawai Hiroya 神戸大学, 医学研究科, 客員教授 (20346266)
• Co-Investigator(Kenkyū-buntansha): 原 哲也 神戸大学, 医学部附属病院, 助教 (70547504)
• Project Period (FY): 2016-10-21 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 血管新生

Outline of Final Research Achievements

（A)　We investigated the role of JCAD in the pathogenesis of angiogenesis in vitro. In HUVEC cells, knock-down of JCAD induced the significant decrease of Tube formation, viability assesed by WST-1.
(B) Role of JCAD in the angiogenesis in vivo. We used tumor growth model, and compared the angiogenesis between JCAD-/- mouse and WT mice. We observed significant decrease of tumor angiogenesis and impaired angiogenesis maturation assessed by SMA satining.

Academic Significance and Societal Importance of the Research Achievements

近年のヒトゲノムワイド関連研究(GWAS)により、心筋梗塞と関連する因子として、JCAD（旧名KIAA1462) が新規に同定された。しかしながら、JCADが心筋梗塞の発症を制御する分子機構は全く明らかになっていない。 JCADは血管内皮細胞の接着因子であることから、血管新生を制御していることが推測される。本研究の成果により、JCADと心筋梗塞との関連が明らかとなれば、将来的にはJCADをターゲットとした新たな治療戦略の確立や、JCAD遺伝子多型によるテーラーメイド医学への応用が期待できる。

Research Products

• [Journal Article] Targeted Disruption of JCAD (Junctional Protein Associated With Coronary Artery Disease)/KIAA1462, a Coronary Artery Disease?Associated Gene Product, Inhibits Angiogenic Processes In Vitro and In Vivo (2017)
  • Author(s): Hara Tetsuya、Monguchi Tomoko、Iwamoto Noriko、Akashi Masaya、Mori Kenta、Oshita Toshihiko、Okano Mitsumasa、Toh Ryuji、Irino Yasuhiro、Shinohara Masakazu、Yamashita Yui、Shioi Go、Furuse Mikio、Ishida Tatsuro、Hirata Ken-ichi
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology Volume: 37 Issue: 9 Pages: 1667-1673
  • DOI: 10.1161/atvbaha.117.309721
  • Peer Reviewed