Homeostasis of vascular vessels and prevention of atherosclerosis by vasohibin-1

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590821
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Tohoku University
• Principal Investigator: MIYASHITA Hiroki 東北大学, 加齢医学研究所, 助教 (80302222)
• Co-Investigator(Kenkyū-buntansha): SATO Yasufumi 東北大学, 加齢医学研究所, 教授 (50178779)
• Project Period (FY): 2010 – 2012
• Keywords: (1)バソヒビン / (2)血管新生抑制因子 / (3)細胞の老化 / (4)動脈硬化

Research Abstract

Vasohibin-1 (VASH1) is isolated as an endothelial cell (EC)-produced angiogenesis inhibitor. We questioned whether VASH1 plays any role besides angiogenesis inhibition, knocked-down or overexpressed VASH1 in ECs, and examined the changes of EC property. Knock-down of VASH1 induced premature senescence of ECs, and those ECs were easily killed by cellular stresses. In contrast, overexpression of VASH1 made ECs resistant to premature senescence and cell death caused by cellular stresses. The synthesis of VASH1 was regulated by HuR-mediated post-transcriptional regulation. We sought to define the underlying mechanism. VASH1 increased the expression of (superoxide dismutase2) SOD2, an enzyme known to quench reactive oxygen species (ROS). Simultaneously, VASH1 augmented the synthesis of sirtuin 1 (SIRT1), an anti-aging protein, which improved stress tolerance.Paraquat generates ROS and causes organ damage when administered in vivo. More VASH1 (+/-) mice died due to acute lung injury caused by paraquat. Intratracheal administration of an adenovirus vector encoding human VASH1 augmented SOD2 and SIRT1 expression in the lungs and prevented acute lung injury caused by paraquat. Thus, VASH1 is a critical factor that improves the stress tolerance of ECs viathe induction of SOD2 and SIRT1.

Research Products

• [Journal Article] angiogenesis inhibitor vasohibin-1 enhances stress resistance of endothelial cells via induction of SOD2 and SIRT1 (2012)
  • Author(s): Miyashita H, Watanabe T, Hayashi H, Suzuki Y, Nakamura T, Ito S, Ono M,Hoshikawa Y, Okada Y, Kondo T, Sato Y.
  • Journal Title: PLoS One Volume: 7 Pages: e46459
• [Journal Article] Mutual Balance betweenVasohibin-1 and Soluble VEGFR-1 inEndothelial Cells (2011)
  • Author(s): Miyashita H, Suzuki H, Ohkuchi A, Sato Y.
  • Journal Title: Pharmaceuticals Volume: 4 Pages: 1551-1577
• [Presentation] 内皮ストレス耐性におけるsplicing variant vasohibin-1の意義 (2010)
  • Author(s): 宮下浩輝、佐藤靖史
  • Organizer: 第18回日本血管生物医学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2010-12-01