Low Shear Stress Inhibited Endothelial Cell Autophagy Through TET2 Downregulation.
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/cm(2)) obviously decreased compared with those under physiological shear stress (15 dyne/cm(2)), 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.
Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, 421001, People's Republic of China.
Qin
Q
Yang
Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, 421001, People's Republic of China.
Xiaohong
X
Li
Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, 421001, People's Republic of China.
Rongqing
R
Li
Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, 421001, People's Republic of China.
Juan
J
Peng
Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, 421001, People's Republic of China.
Zuo
Z
Wang
Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, 421001, People's Republic of China.
Zhisheng
Z
Jiang
Department of Physiology & Institute of Neuroscience, Medical School, University of South China, Hengyang, 421001, People's Republic of China.
Xiaoqing
X
Tang
Affiliated Hospital Xiang Nan University, Chengzhou, 423000, People's Republic of China. pengzhaocz201@126.com.
Zhao
Z
Peng
Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China. wangyuyc@hotmail.com.
Yu
Y
Wang
Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, 421001, People's Republic of China. weizhonghua99@126.com.
Dangheng
D
Wei
D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D049308:Dioxygenases; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D033081:Shear Strength; D013314:Stress, Mechanical
D000071186:Beclin-1; D004268:DNA-Binding Proteins; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C551914:Tet2 protein, mouse; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
Atherosclerosis; Autophagy; Endothelial cell; Low shear stress; Ten-eleven translocation 2 protein