Abstract
ObjectiveTo investigate the effects of miR-218 on expression of hypoxia-inducible factors 1α (HIF-1α), vascular endothelial growth factor (VEGF) and cell apoptosis in normal mice aortic endothelial cells under intermittent hypoxia (IH) condition.MethodsAnti-miR-218 inhibitor, miR-negative control and miR-218 mimic were used to tranfect the cells in different groups under IH condition. Both RT-PCR and Western blot were used to determine the expressions of HIF-1α and VEGF. Akt, p-Akt and cell apoptosis related proteins bcl-2, bax and caspase-3 and roundabout 1 (Robo1) were measured using Western blot. Cell apoptosis was evaluated by flow cytometry. Statistical analysis was performed using SPSS 18.0.ResultsExpression of miR-218 was significantly up-regulated in the IH group and was significantly inhibited when cells were transfected with miR-218 inhibitor. Down regulation of miR-218 could reduce the expression of HIF-1α and VEGF under intermittent hypoxia condition. In cells transfected with miR-218 mimic, expression of HIF-1α and VEGF significantly increased compared with the control. However, when treated with LY294002, the expression of HIF-1α and VEGF both decreased. Apoptosis assay showed that down regulation of miR-218 could inhibit intermittent hypoxia induced cell apoptosis, decrease expression of caspase-3 and bax and increase expression of bcl-2 under intermittent hypoxia condition. At last, silencing Robo1 could significantly enhance the expression of HIF-1α under IH condition.ConclusionInhibition of miR-218 could reduce the expression of HIF-1α and protect against IH-induced apoptosis in mice aortic endothelial cells. The effects were associated with PI3K/AKT pathway and might through targeting of Robo1.
Highlights
Obstructive Sleep Apnea (OSA), of which the main symptom is the repeated episodes of upper airway obstruction during sleep, is recognized as a significant and highly prevalent health problem with cardiovascular and metabolic morbidity, as well as its prominent cognitive and behavioral implications [1]
Down regulation of miR-218 could reduce the expression of hypoxiainducible factors 1α (HIF-1α) and vascular endothelial growth factor (VEGF) under intermittent hypoxia condition
In cells transfected with miR-218 mimic, expression of HIF-1α and VEGF significantly increased compared with the control
Summary
Obstructive Sleep Apnea (OSA), of which the main symptom is the repeated episodes of upper airway obstruction during sleep, is recognized as a significant and highly prevalent health problem with cardiovascular and metabolic morbidity, as well as its prominent cognitive and behavioral implications [1]. IH is associated with lots of biological process, including neurobehavioral impairments, increased apoptosis and www.impactjournals.com/oncotarget oxidant stress and inflammation [4]. Cell apoptosis induced by IH is one of the main problems in OSA patients [4, 5]. Several studies suggested that IH influenced a variety of transcription factors, including the hypoxiainducible factors 1α (HIF-1α), nuclear factor of activated T cells, activator protein 1 and NF-kB [6]. Recent studies have shown that HIF-1α is one of the major molecular mechanisms which increases ROS generation, regulates the expression of downstream target genes and mediates cell apoptosis caused by IH-induced endothelial injury [7]. What’s more, scientists found that IH could upregulate the level of HIF-1α, and the expression of vascular endothelial growth factor (VEGF) [8, 9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
