Endothelial cell autophagy in chronic intermittent hypoxia is impaired by miRNA‐30a‐mediated translational control of Beclin‐1

Abstract

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. K E Y W O R D S autophagy, Beclin-1, chronic intermittent hypoxia, endothelial cells, obstructive sleep apnea

miR-146a-5p Mediates Intermittent Hypoxia-Induced Injury in H9c2 Cells by Targeting XIAP

“…It was reported that the miR-193 inhibitor could reverse IH-induced apoptosis and autophagy relative protein expression in mouse aortic endothelial cells [26]. Recently, downregulation of miR-30a seemed to enhance IH-associated endothelial cell autophagy by increasing Beclin-1 [27]. Our results showed miR-146a-5p was markedly increased after IH; therefore, we chose miR-146a-5p for this study and investigated the relationship between miR-146a-5p and myocardial injury under IH condition.…”

Exosomes Derived From Epigallocatechin Gallate-Treated Cardiomyocytes Attenuated Acute Myocardial Infarction by Modulating MicroRNA-30a

“…They are positively or inversely related to autophagy activity. Several studies have shown that cell autophagy may be attenuated by miR-30a-mediated translational control of Beclin-1, and miR-30a directly binds to the 3′-UTR of Beclin-1 gene (Bi et al, 2019). Therefore, Beclin-1 is also a direct target of miR-30a to inhibit autophagy.…”

MicroRNA-421 protects against chronic intermittent hypoxia-induced vascular endothelial cell injury by targeting TLR4

“…It is well accepted that OSAS is chronic respiratory disease that can induce CIH, which may result in endothelial dysfunction and multiple organ damage [3,4,6]. Many miRNAs, such as miR-664a-3p, miR-630, and miR-30a, play important roles during the development of OSAS [6,13,14]. In this study, CIH-treated endothelial cells had lower viability and decreased miR-421 levels compared to control cells, suggesting that miR-421 may exert protective effects on CIH-treated endothelial cells.…”

“…Importantly, chronic intermittent hypoxia (CIH) is a characteristic of OSAS [4] and a key factor of oxidative stress that induce the release of reactive oxygen species (ROS), which subsequently results in systemic inflammation [1]. Previous studies confirmed that CIH is responsible for the dysfunction and injury of endothelial cell [6,7].…”

“…It has also been reported that miR-630 may play important roles in OSAS-induced endothelial dysfunction [14]. The suppression of miR-30a inhibits CIHinduced endothelial cell damage [6]. In particular, miR-421 plays key roles in various diseases such as cancer, epilepsy, and nonalcoholic fatty liver disease (NAFLD) [15][16][17].…”