Effect of hypoxia on endothelial growth factor expression in vascular intimal smooth muscle cells and cell functions of brain arteriovenous malformation swine models

Abstract

Objective To investigate the effect of hypoxia on endothelial growth factor (VEGF) expression in vascular intimal smooth muscle cells (VSMC) and function of VSMC of swine models of brain arteriovenous malformations (BAVM). Methods The stable swine models of BAVM were established; separation of cerebral microvascular network (RM) was performed and VSMC was selected and primarily cultured. VSMC from the above models and normal swines were divided into four groups: group A, VSMC from normal swines cultured at 21% O2; group B, VSMC from models cultured at 21% O2; group C, VSMC from normal swines cultured at 1% O2; group D, VSMC from models cultured at 1% O2. Quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting were used to validate the mRNA and protein VEGF expressions in VSMC; TUNNEL was used to detect the apoptosis of VSMC, and Transwell assay was used to determine the VSMC invasion. Results (1) VSMC density in the four groups was 71.65±4.22, 158.24±9.87, 95.33±7.21 and 299.80±13.23 cells/field in group A-D, with significant differences (F=119.351, P=0.000). (2) VEGF mRNA expression quantity in the four groups was 1.93±0.77, 4.51±1.25, 2.87±1.94 and 8.03±1.74 in group A-D, with significant differences (F=119.351, P=0.000); that in group B-D was significantly higher than that in group A (P 0.05); at the 72 h, the number of apoptosis and invasion cells in group A was significantly decreased as compared with those in group B, C and D (P<0.05). Conclusion Hypoxia can increase the VEGF expression, aggravate the apoptosis and invasion of VSMC, and accelerate the formation of vascular malformation in BAVM models. Key words: Hypoxia; Endangium; Vascular smooth muscle cell; Vascular endothelial growth factor