Research Papers:
Endothelial cell autophagy in chronic intermittent hypoxia is impaired by miRNA-30a-mediated translational control of Beclin-1
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Abstract
Kai-Xiong Liu1,2,3, Qin Chen4, Gong-Ping Chen1,2,3, Jian-Chai Huang1,2,3, Jie-Feng Huang1,2,3, Xin-Ru He1,2,3, Ting Lin1,2,3 and Qi-Chang Lin1,2,3
1Department of Respiratory Disease, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
2Laboratory of Respiratory Disease of Fujian Medical University, Fuzhou 350005, China
3Fujian Provincial Sleep-Disordered Breathing Clinic Center, Fuzhou 350005, China
4Integrated Chinese and Western Medicine Colleges, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
Correspondence to:
Qi-Chang Lin, email: [email protected]
Keywords: chronic intermittent hypoxia (CIH); obstructive sleep apnea (OSA); autophagy; Beclin-1; miR-30a
Received: August 21, 2017 Accepted: September 03, 2017 Published: January 02, 2018
ABSTRACT
Chronic intermittent hypoxia (CIH) in obstructive sleep apnea causes damages of aortic endothelial cells, which predisposes development of many cardiovascular diseases. Recently, both altered expression of microRNAs (miRNAs) and impaired autophagy were found to be associated with endothelial cell dysfunction in CIH. However, the exact molecular regulatory pathway has not been determined. Here, we addressed this question. In a mouse model of CIH, we detected significant upregulation of miR-30a, a miRNA that targets 3′-UTR of autophagy-associated protein 6 (Beclin-1) mRNA to suppress the protein translation, which subsequently attenuated the endothelial cell autophagy against cell death. Indeed, unlike Beclin-1 mRNA, the Beclin-1 protein in endothelial cells did not increase after CIH. Suppression of miR-30a by expression of antisense of miR-30a significantly increased Beclin-1 levels to enhance endothelial cell autophagy in vitro and in vivo, which improved endothelial cell survival against CIH. Together, these data suggest that endothelial cell autophagy in CIH may be attenuated by miR-30a-mediated translational control of Beclin-1, as an important cause of endothelial cell dysfunction and damage.
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