Hypoxia-inducible factor-1α relieves mitochondrial damage in hypoxic vascular endothelial cells

Abstract

Objective To investigate the protective mechanism of hypoxia-inducible factor-1α (HIF-1α) in vascular endothelial cells under hypoxia. Methods 1. After a hemorrhagic shock model was established in mice, the vascular endothelial cells were sorted in a shock group (n=3) and a sham operation group (n=3) for RNA-sequencing to analyze the main differential molecules. 2. The expression of HIF-1α and glucose transporter-1 (GLUT1) was measured in human umbilical vein endothelial cells (HUVECs) and the mitochondrial membrane potentials were detected in a control group (normal culture, n=3) and a hypoxia group (hypoxia culture for 6 h, n=3). 3. The HUVECs cells were transfected with HIF-1α siRNA for 48 h to interfere with HIF-1α expression, and the control group(n=3) was transfected with control siRNA. The expression of HIF-1α was detected to determine the interference effect. The mRNA and protein expression of GLUT1 was detected in the interference and the control groups after 6 h of hypoxia culture. The mitochondrial membrane potential was detected by fluorescent probe method. Results 1. The tran-scriptome sequencing in the vascular endothelial cells in the shock and sham operation groups indicated 25 genes with significant differences. The HIF-1α expression was significantly increased in the shock group (111.70±15.97) than in the sham operation group (53.49±3.26) (P=0.023). 2. The expression of HIF-1α and GLUT1 in the HUVECs cells was significantly increased in the hypoxia group compared with the control group (P 0.05). However, after hypoxia culture for 6 h, there was a significant difference in the mitochondrial membrane potential between the interference group (0.514±0.018) and the control group (0.769±0.044) (P<0.05), also indicating aggravated damage. Conclusions The expression of HIF-1α may be significantly increased in hemorrhagic shock. In HUVECs under hypoxia, HIF-1α may up-regulate the expression of GLUT1, promote glucose transport, improve mitochondrial damage and protect vascular endothelial cells. Thus, targeting HIF-1α may contribute to the treatment of hemorrhagic shock. Key words: Hypoxia-inducible factor-1α; Vascular endothelial cells; Mitochondria