Angiogenesis Inhibitor Vasohibin-1 Enhances Stress Resistance of Endothelial Cells via Induction of SOD2 and SIRT1

Hiroki Miyashita, Tatsuaki Watanabe, Hideki Hayashi, Yasuhiro Suzuki, Takanobu Nakamura, Soichi Ito, Manabu Ono, Yasushi Hoshikawa, Yoshinori Okada, Takashi Kondo, Yasufumi Sato

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42 Citations (Scopus)

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 dismutase 2) 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 via the induction of SOD2 and SIRT1.

Original languageEnglish
Article numbere46459
JournalPloS one
Volume7
Issue number10
DOIs
Publication statusPublished - 08-10-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Miyashita, H., Watanabe, T., Hayashi, H., Suzuki, Y., Nakamura, T., Ito, S., Ono, M., Hoshikawa, Y., Okada, Y., Kondo, T., & Sato, Y. (2012). Angiogenesis Inhibitor Vasohibin-1 Enhances Stress Resistance of Endothelial Cells via Induction of SOD2 and SIRT1. PloS one, 7(10), [e46459]. https://doi.org/10.1371/journal.pone.0046459