Heme relieves the inhibition of proliferation, migration and angiogenesis of HMEC-1 under hyperoxia by inhibiting BACH1

Abstract

Background The relatively hyperoxia inhibited vascular endothelial growth factor (VEGF) in retina is the main cause of angiogenesis retardation in phase I retinopathy of prematurity (ROP). Human retinal angiogenesis is related to the proliferation, migration and angiogenesis of microvascular endothelial cells. Previous studies have confirmed that BTB and CNC homology l (BACH1) can inhibit VEGF and angiogenesis, while heme can specifically degrade BACH1. However, the effect of heme on endothelial cells and ROP remains unknown. Methods In this report, we established a model of human microvascular endothelial cells (HMEC-1) induced by 40% hyperoxia to simulate the relatively hyperoxia of phase I ROP. Meanwhile, heme was added to investigate the effects on the growth and viability of HMEC-1. Cell counting kit 8 (CCK8) and 5-ethynyl-2′-deox-yuridine (EDU) methods were used to detect the proliferation ability. Cell scratch test and matrigel matrix glue were used to detect the migration or angiogenesis ability. Western blot and immunofluorescence methods were used to detect the relative protein expression of BACH1 and VEGF. Results The proliferation, migration and angiogenesis of HMEC-1 were inhibited under hyperoxia. Moderate heme can promote endothelial cell proliferation, while excessive can inhibit, 20 µM heme could inhibit the expression of BACH1, promote the expression of VEGF, and relieve the inhibition of proliferation, migration and angiogenesis induced by hyperoxia in HMEC-1. Conclusions 20 µM heme can relieve the inhibitory effects induced by hyperoxia, via the mechanism of promoting VEGF by inhibiting BACH1 in HMEC-1, and maybe a potential medicine for retinal angiogenesis retardation induced by relatively hyperoxia in phase I ROP.