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Annals of Biomedical Engineering

, Volume 44, Issue 7, pp 2218–2227 | Cite as

Low Shear Stress Inhibited Endothelial Cell Autophagy Through TET2 Downregulation

  • Qin Yang
  • Xiaohong Li
  • Rongqing Li
  • Juan Peng
  • Zuo Wang
  • Zhisheng Jiang
  • Xiaoqing Tang
  • Zhao Peng
  • Yu Wang
  • Dangheng Wei
Article

Abstract

Low shear stress plays a crucial role in the initiation and progression of atherosclerotic lesions. However, the detailed mechanisms of these processes remain unclear. In this study, the effect of low shear stress on endothelial cell autophagy and its potential mechanism were investigated. Results showed autophagy dysfunction and ten-eleven translocation 2 (TET2) protein downregulation during atherosclerotic lesion progression. Autophagic markers BECLIN 1 and LC3II/LC3I under low shear stress (5 dyne/cm2) obviously decreased compared with those under physiological shear stress (15 dyne/cm2), whereas autophagic substrate p62 increased. TET2 expression was also downregulated under low shear stress. Endothelial cell autophagy was improved with TET2 overexpression but was impaired by TET2 siRNA treatment. Moreover, TET2 overexpression upregulated the expression of endothelial cell nitric oxide synthase (eNOS) and downregulated the expression of endothelin-1 (ET-1). TET2 siRNA further attenuated eNOS expression and stimulated ET-1 expression. Overall, the results showed that low shear stress downregulated endothelial cell autophagy by impaired TET2 expression, which might contribute to the atherogenic process.

Keywords

Low shear stress Autophagy Ten-eleven translocation 2 protein Endothelial cell Atherosclerosis 

Notes

Acknowledgments

The present research is supported by the National Natural Science Foundation of China (81370378, 30800449), the construct program of the key discipline in Hunan province and Zhengxiang Scholar Program of University of South China (2014-004).

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Copyright information

© Biomedical Engineering Society 2015

Authors and Affiliations

  1. 1.Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan ProvinceUniversity of South ChinaHengyangPeople’s Republic of China
  2. 2.Affiliated Hospital Xiang Nan UniversityChengzhouPeople’s Republic of China
  3. 3.Department of Neurosurgery, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  4. 4.Department of Physiology & Institute of Neuroscience, Medical SchoolUniversity of South ChinaHengyangPeople’s Republic of China

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