Science China Life Sciences

, Volume 55, Issue 6, pp 467–473

Endothelium-specific SIRT1 overexpression inhibits hyperglycemia-induced upregulation of vascular cell senescence

  • HouZao Chen
  • YanZhen Wan
  • Shuang Zhou
  • YunBiao Lu
  • ZhuQin Zhang
  • Ran Zhang
  • Feng Chen
  • DeLong Hao
  • Xiang Zhao
  • ZhiChen Guo
  • DePei Liu
  • ChihChuan Liang
Open AccessCover Article

DOI: 10.1007/s11427-012-4329-4

Cite this article as:
Chen, H., Wan, Y., Zhou, S. et al. Sci. China Life Sci. (2012) 55: 467. doi:10.1007/s11427-012-4329-4

Abstract

The rapidly increasing prevalence of diabetes mellitus worldwide is one of the most serious and challenging health problems in the 21st century. Mammalian sirtuin 1 (SIRT1) has been shown to decrease high-glucose-induced endothelial cell senescence in vitro and prevent hyperglycemia-induced vascular dysfunction. However, a role for SIRT1 in prevention of hyperglycemia-induced vascular cell senescence in vivo remains unclear. We used endothelium-specific SIRT1 transgenic (SIRT1-Tg) mice and wild-type (WT) mice to construct a 40-week streptozotocin (STZ)-induced diabetic mouse model. In this mode, 42.9% of wild-type (WT) mice and 38.5% of SIRT1-Tg mice were successfully established as diabetic. Forty weeks of hyperglycemia induced significant vascular cell senescence in aortas of mice, as indicated by upregulation of expression of senescence-associated markers including p53, p21 and plasminogen activator inhibitor-1 (PAI-1). However, SIRT1-Tg diabetic mice displayed dramatically decreased expression of p53, p21 and PAI-1 compared with diabetic WT mice. Moreover, manganese superoxide dismutase expression (MnSOD) was significantly downregulated in the aortas of diabetic WT mice, but was preserved in diabetic SIRT1-Tg mice. Furthermore, expression of the oxidative stress adaptor p66Shc was significantly decreased in aortas of SIRT1-Tg diabetic mice compared with WT diabetic mice. Overall, these findings suggest that SIRT1-mediated inhibition of hyperglycemia-induced vascular cell senescence is mediated at least partly through the reduction of oxidative stress.

Keywords

SIRT1hyperglycemiavascular cell senescence
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© The Author(s) 2012

Authors and Affiliations

  • HouZao Chen
    • 1
  • YanZhen Wan
    • 1
  • Shuang Zhou
    • 1
    • 2
  • YunBiao Lu
    • 1
  • ZhuQin Zhang
    • 1
  • Ran Zhang
    • 1
  • Feng Chen
    • 1
  • DeLong Hao
    • 1
  • Xiang Zhao
    • 1
  • ZhiChen Guo
    • 1
  • DePei Liu
    • 1
  • ChihChuan Liang
    • 1
  1. 1.National Laboratory of Medical Molecular Biology, Institute of Basic Medical SciencesChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
  2. 2.Department of Rheumatology and ImmunologyPeking Union Medical College HospitalBeijingChina