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Endothelial cell autophagy in chronic intermittent hypoxia is impaired by miRNA‐30a‐mediated translational control of Beclin‐1
Author(s) -
Bi Rongrong,
Dai Yancheng,
Ma Zifeng,
Zhang Shaoyan,
Wang Lei,
Lin Qichang
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27708
Subject(s) - autophagy , endothelial stem cell , microrna , downregulation and upregulation , microbiology and biotechnology , messenger rna , biology , hypoxia (environmental) , cell , untranslated region , endothelial dysfunction , three prime untranslated region , programmed cell death , chemistry , in vitro , endocrinology , apoptosis , biochemistry , gene , organic chemistry , oxygen
Chronic intermittent hypoxia (CIH) in obstructive sleep apnea causes damage of aortic endothelial cells, which predisposes the 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 address this question. In a mouse model of CIH, we detected significant upregulation of miR‐30a, a miRNA that targets 3′‐untranslated region of autophagy‐associated protein 6 (Beclin‐1) messenger RNA (mRNA) for suppressing 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.