angiogenesis inhibitor vasohibin-1 enhances stress resistance of endothelial cells via induction of sod2 and sirt1内皮细胞的血管生成抑制剂vasohibin-1增强抗压性通过感应sod2 sirt1.pdfVIP

Angiogenesis Inhibitor Vasohibin-1 Enhances Stress Resistance of Endothelial Cells via Induction of SOD2 and SIRT1 1. 1,2. 1¤ 1 1 Hiroki Miyashita , Tatsuaki Watanabe , Hideki Hayashi , Yasuhiro Suzuki , Takanobu Nakamura , 1 1 2 2 2 1 Soichi Ito , Manabu Ono , Yasushi Hoshikawa , Yoshinori Okada , Takashi Kondo , Yasufumi Sato * 1 Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan, 2 Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan 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 (+/ 2) mice died du