The Effect of MiR-17-5p on ox-LDL-Induced Endothelial Cell Injury by Regulating the PPARγ/ABCA1 Signaling Pathway
XU Hang1, ZHANG Fulong2, WANG Huan3*
This study aims to investigate the effect of miR-17-5p on ox-LDL (oxidized low-density lipoprotein)-induced vascular endothelial cell injury by regulating the PPARγ (peroxisome proliferator activated receptor-γ)/ABCA1 (ATP binding cassette transporter A1) signaling pathway. HAEC (human aortic endothelial cell) were assigned into control group, ox-LDL group, inhibitor NC group, miR-17-5p inhibitor group, and miR-17-5p inhibitor+GW9662 group. All other groups except the control group were induced HAEC injury using ox- LDL. CCK-8 method was used to detect HAEC proliferation. Flow cytometry was used to detect HAEC apoptosis. The angiogenesis experiment detected the angiogenesis. Reagent kits were used to determine the activities of MDA (malondialdehyde), SOD (superoxide dismutase), and GSH-Px (glutathione peroxidase) in HAEC. qRT-PCR was
used to detect the mRNA expression levels of miR-17-5p, PPARγ, and ABCA1 in HAEC. Western blot was used to analyze PPARγ and ABCA1 protein levels in HAEC. Dual luciferase reporter gene was used to detect the relationship between miR-17-5p and ABCA1. Compared with the control group, the D450 value of HAEC in the ox-LDL group was reduced, the SOD and GSH-Px activities decreased, the expression levels of PPARγ, ABCA1 mRNAs and proteins decreased, while the apoptosis rate, miR-17-5p, and MDA levels increased, blood vessel formation reduced (P<0.05). Compared with the inhibitor NC group, the D450 value of HAEC in miR-17-5p inhibitor group was increased, the SOD and GSH-Px activities increased, PPARγ, ABCA1 mRNA and protein expression increased, while the apoptosis rate, miR-17-5p and MDA levels reduced, blood vessel formation increased (P<0.05). Compared with the miR-17-5p inhibitor group, the D450 value of HAEC in miR-17-5p inhibitor+GW9662 group was
reduced, the SOD and GSH-Px activities decreased, the expression levels of PPARγ, ABCA1 mRNAs and proteins decreased, while the apoptosis rate, miR-17-5p, and MDA levels increased, blood vessel formation reduced (P<0.05). MiR-17-5p may exacerbate ox-LDL-induced HAEC injury by inhibiting the PPARγ/ABCA1 signaling pathway.
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