Hypoxia-inducible factor-1α expression in experimental cirrhosis: correlation with vascular endothelial growth factor expression and angiogenesis
Abstract:Bozova S, Elpek GO. Hypoxia-inducible factor-1α expression in experimental cirrhosis: correlation with vascular endothelial growth factor expression and angiogenesis. APMIS 2007;115:795–801.
Angiogenesis progresses together with fibrogenesis during chronic liver injury. Hypoxia-inducible factor-1α (HIF-1α), a master regulator of homeostasis, plays a pivotal role in hypoxia-induced angiogenesis through its regulation of vascular endothelial growth factor (VEGF). The association between hypoxia, angiogenesis and VEGF expression has been demonstrated in experimental cirrhosis. However, expression of HIF-1α has yet to be reported. The aim of this study was to investigate the significance of HIF-1α expression during experimental liver fibrosis and the relationships between HIF-1α expression, VEGF expression and angiogenesis. Cirrhosis was induced in male Wistar rats by intraperitoneal administration of diethyl nitrosamine (DEN) (100 mg/kg, once a week). The serial sections from liver tissues were stained with anti-HIF-1α, anti-VEGF and anti-CD34 antibodies before being measured by light microscopy. Our results showed that HIF-1α expression gradually increases according to the severity of fibrosis (p<0.01). Moreover, its expression was found to be correlated with angiogenesis (r=0.916) and VEGF expression (r=0.969). The present study demonstrates that HIF-1α might have a role in the development of angiogenesis via regulation of VEGF during experimental liver fibrogenesis and suggests that this factor could be a potential target in the manipulation of angiogenesis in chronic inflammatory diseases of the liver.