3099

HK2

HKII|HXK2;hexokinase 2;HK2;hexokinase 2

HK II|hexokinase type II|hexokinase-2|hexokinase-2, muscle|muscle form hexokinase

2p13

protein-coding

Count: Hk2; 25059

INTRODUCTION: The role of hypoxia-inducible factor-1alpha (HIF-1alpha) in pulmonary vascular remodeling is still undetermined. The objective of this study is to investigate the expression of HIF-1alpha and its role in proliferating neointimal lesions in a rat model of pulmonary arterial hypertension induced by monocrotaline (MCT) administration after left pneumonectomy. METHODS: The rats were subjected to MCT (60 mg/kg, subcutaneously) 7 days after left pneumonectomy or sham surgery; controls with vehicle treatment after left pneumonectomy or sham surgery were also studied. On day 35, hemodynamic parameters of the rats were measured. The right lower lobes of the lungs were fixed for morphometric analysis. The expression of proliferating cell nuclear antigen and survivin was detected with Western blot. The expressions of HIF-1alpha and hexokinase-2 (HK-2) were detected with Western blot and immunohistochemistry assay. RESULTS: The rats treated with MCT after pneumonectomy developed severe pulmonary arterial hypertension and marked medial thickening on day 35. The neointimal lesions in pulmonary arterioles were observed only in MCT-treated pneumonectomized rats. The severely injured pulmonary arterioles (intimal proliferation causing greater than 50% luminal occlusion) accounted for 40% of all the measured arterioles in rats treated by MCT after pneumonectomy. The intriguing finding showed that HIF-1alpha was predominantly expressed in neointimal lesion areas, paralleled with the increased expression of HK-2 in MCT-treated pneumonectomized rats, which was not observed in rats undergoing MCT treatment alone. CONCLUSIONS: The activation of HIF-1alpha/HK-2 axis is probably the key mediator responsible for the neointimal lesion formation in MCT-treated pneumonectomized rats.

INTRODUCTION: The role of hypoxia-inducible factor-1alpha (HIF-1alpha) in pulmonary vascular remodeling is still undetermined. The objective of this study is to investigate the expression of HIF-1alpha and its role in proliferating neointimal lesions in a rat model of pulmonary arterial hypertension induced by monocrotaline (MCT) administration after left pneumonectomy. METHODS: The rats were subjected to MCT (60 mg/kg, subcutaneously) 7 days after left pneumonectomy or sham surgery; controls with vehicle treatment after left pneumonectomy or sham surgery were also studied. On day 35, hemodynamic parameters of the rats were measured. The right lower lobes of the lungs were fixed for morphometric analysis. The expression of proliferating cell nuclear antigen and survivin was detected with Western blot. The expressions of HIF-1alpha and hexokinase-2 (HK-2) were detected with Western blot and immunohistochemistry assay. RESULTS: The rats treated with MCT after pneumonectomy developed severe pulmonary arterial hypertension and marked medial thickening on day 35. The neointimal lesions in pulmonary arterioles were observed only in MCT-treated pneumonectomized rats. The severely injured pulmonary arterioles (intimal proliferation causing greater than 50% luminal occlusion) accounted for 40% of all the measured arterioles in rats treated by MCT after pneumonectomy. The intriguing finding showed that HIF-1alpha was predominantly expressed in neointimal lesion areas, paralleled with the increased expression of HK-2 in MCT-treated pneumonectomized rats, which was not observed in rats undergoing MCT treatment alone. CONCLUSIONS: The activation of HIF-1alpha/HK-2 axis is probably the key mediator responsible for the neointimal lesion formation in MCT-treated pneumonectomized rats.