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Low Shear Stress Inhibited Endothelial Cell Autophagy Through TET2 Downregulation

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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.

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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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    Authors and Affiliations

    1. Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, 421001, People’s Republic of China

      Qin Yang, Xiaohong Li, Rongqing Li, Juan Peng, Zuo Wang, Zhisheng Jiang & Dangheng Wei

    2. Affiliated Hospital Xiang Nan University, Chengzhou, 423000, People’s Republic of China

      Zhao Peng

    3. Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China

      Yu Wang

    4. Department of Physiology & Institute of Neuroscience, Medical School, University of South China, Hengyang, 421001, People’s Republic of China

      Xiaoqing Tang

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    1. Qin Yang
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    Correspondence to Zhao Peng, Yu Wang or Dangheng Wei.

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    Associate Editor Estefanía Peña oversaw the review of this article.

    Qin Yang, Xiaohong Li, and Rongqing Li have contributed equally to this work.

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    Yang, Q., Li, X., Li, R. et al. Low Shear Stress Inhibited Endothelial Cell Autophagy Through TET2 Downregulation. Ann Biomed Eng 44, 2218–2227 (2016). https://doi.org/10.1007/s10439-015-1491-4

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