The Effect of Autophagy Intervention on Vascular Endothelial Cells eNOS and ET-1 Expression Under Low Shear Stress
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    Abstract:

    Aim To explore the effect of autophagy intervention on endothelial cells endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) expression under low shear stress. Methods ApoE-/- mice were fed with high fat diet for 12 weeks. HE staining was used to detect the pathological changes of aortic sinus. Immunohistochemistry was applied to detect the protein expression of autophagy markers Beclin1, microtubule-associated protein 1 light chain 3 (LC3Ⅱ) and p62. Human umbilical vein endothelial cells (HUVEC) and separated New Zealand rabbits common carotid arteries were placed into an in vivo perfusion system with low shear stress (5 dyne/cm2) or normal shear stress (15 dyne/cm2) for 1 h, then the expression of Beclin1, LC3Ⅱ/LC3Ⅰ and p62 was measured using Western blot. After treated with 5 dyne/cm2 for 1 h followed with or without rapamycin or 3-methyladenine (3-MA) for 30 min, the expression of eNOS and ET-1 in human vascular endothelial cells and common arteries of New Zealand rabbits was detected. Results The expression of Beclin1, LC3Ⅱ and p62 was significantly increased in atherosclerotic plaque. Compared with 15 dyne/cm2 treatment group, the expression of Beclin1, LC3Ⅱ and p62 was significantly increased in 5 dyne/cm2 treatment group (P<0.05). The autophagy inducer rapamycin up-regulated the eNOS expression and inhibited the ET-1 expression in both 5 dyne/cm2 treated HUVEC and common carotid arteries, whereas autophagy inhibitor 3-MA further inhibited eNOS expression and increased the ET-1 expression. Conclusion The inhibition of autophagy might contribute to the decreased expression of eNOS and the increased expression of ET-1 under low shear stress, which was improved by promoting autophagy.

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LI Xiao-Hong, GUO Feng-Xia, YANG Qin, LI Rong-Qing, ZHAO Zhan-Zhi, ,WEI Dang-Heng. The Effect of Autophagy Intervention on Vascular Endothelial Cells eNOS and ET-1 Expression Under Low Shear Stress[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2014,22(9):875-880.

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  • Received:June 09,2014
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