Vasohibin induces prolyl hydroxylase-mediated degradation of hypoxia-inducible factor-1α in human umbilical vein endothelial cells

Vasohibin is thought to be an important negative feedback regulator of angiogenesis that is selectively induced in endothelial cells by VEGF. Here, we assessed the role of vasohibin on HIF-1α expression under oxidative stress induced by hydrogen peroxide (H2O2) in HUVEC. VEGF induced significant cell growth that was associated with an increase in vasohibin expression. Following H2O2-pretreatment, VEGF further increased cell growth but this was contrastingly associated with a decrease in vasohibin expression when compared with VEGF alone. Interestingly, vasohibin inhibited cell proliferation through degradation of HIF-1α expression during H2O2-pretreatment. Furthermore, vasohibin elevated the expression of prolyl hydroxylase (PHD). These results suggest that vasohibin plays crucial roles as a negative feedback regulator of angiogenesis through HIF-1α degradation via PHD.

► H2O2-pretreatment before VEGF stimulation increased cell growth.
► H2O2-pretreatment before VEGF stimulation decreased vasohibin expression.
► H2O2-mediated degradation of vasohibin protein and mRNA was dose-dependent.
► Vasohibin inhibited cell proliferation through the degradation of HIF-1α expression.
► Vasohibin elevated the expression of PHD, which regulates HIF hydroxylation.