Abstract
Vascular endothelial cell function responds to steady laminar shear stress; however, the underlying mechanisms are not fully elucidated. In the present study, we examined the effect of steady laminar shear stress on vascular endothelial cell autophagy and endothelial cell nitric oxide synthase (eNOS) and endothelin-1 (ET-1) expression using an ex vivo perfusion system. Human vascular endothelial cells and common arteries of New Zealand rabbits were pretreated with or without rapamycin or 3-MA for 30 min. These were then placed in an ex vivo cell perfusion system or an ex vivo organ perfusion system under static conditions (0 dynes/cm2) or steady laminar shear stress (5 or 15 dynes/cm2) for 1 h. In both ex vivo perfusion vascular endothelial cells and vascular vessel segment, steady laminar shear stress promoted autophagy and eNOS expression and inhibited ET-1 expression. Compared with steady laminar shear stress treatment alone, the pretreatment of autophagy inducer rapamycin obviously strengthened the expression of eNOS and decreased the expression of ET-1 in both the 5 and 15 dynes/cm2 treatment groups. Moreover, when pretreated with the autophagy inhibitor 3-MA, the eNOS expression was obviously inhibited and the ET-1 expression was reversed. These findings demonstrate that autophagy is upregulated under steady laminar shear stress, improving endothelial cell maintenance of vascular tone function.
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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 key grant from the National Natural Science Foundation of China (No. 11332003).
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Associate Editor Estefanía Peña oversaw the review of this article.
Fengxia Guo, Xiaohong Li, and Juan Peng contributed equally to this study.
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Guo, F., Li, X., Peng, J. et al. Autophagy Regulates Vascular Endothelial Cell eNOS and ET-1 Expression Induced by Laminar Shear Stress in an Ex Vivo Perfused System. Ann Biomed Eng 42, 1978–1988 (2014). https://doi.org/10.1007/s10439-014-1033-5
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DOI: https://doi.org/10.1007/s10439-014-1033-5