Regulatory mechanism of HIF-1α/HO-1/VEGF-A signaling pathway in immaturity of autogenous arteriovenous fistula

Objective To observe the differences in the expression levels of the hypoxia-inducible factor-1α/heme oxygenase-1/vascular endothelial growth factor A (HIF-1α/HO-1/VEGF-A) signaling pathway under different maturation outcomes of arteriovenous fistula (AVF) in patients with stage 5 chronic kidney disease, and explore the regulatory mechanism of the HIF-1α/HO-1/VEGF-A signaling pathway in the maturation process of AVF.

Methods A total of 45 patients with AVF surgery for stage 5 chronic kidney disease were selected as research objects, vascular specimens were collected during the AVF surgery, and the patients were divided into AVF maturation group (n=35) and AVF poor maturation group (n=10) based on the AVF maturation outcomes within 8 weeks after surgery. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the gene expression levels of HIF-1α, HO-1 and VEGF-A in the HIF-1α/HO-1/VEGF-A signaling pathway; the Western blotting was used to detect the protein expression levels of HIF-1α, HO-1 and VEGF-A; the enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of downstream inflammatory factors such as interleukin-1β (IL-1β), interleukin-8 (IL-8), and transforming growth factor-β (TGF-β).

Results The expression levels of HIF-1α mRNA, HO-1 mRNA, and VEGF-A mRNA in the AVF maturation group were significantly higher than those in the AVF poor maturation group (P < 0.01); the protein expression levels of HIF-1α, HO-1 and VEGF-A in the AVF maturation group were significantly higher than those in the AVF poor maturation group (P < 0.01); the expression levels of IL-1β, IL-8 and TGF-β in the AVF maturation group were significantly lower than those in the AVF poor maturation group (P < 0.01).

Conclusion The upregulation of the HIF-1α/HO-1/VEGF-A signaling pathway is conducive to the early maturation of AVF. The measurement of the expression levels of the HIF-1α/HO-1/VEGF-A signaling pathway has a certain predictive significance for the early maturation outcome of AVF.