Non-hypoxic pathway mediates the induction of hypoxia inducible factor 1 alpha (HIF-1 alpha ) in vascular smooth muscle cells

摘要: Hypoxia-inducible factor-1 (HIF-1) controls the expression of a number genes such as vascular endothelial growth factor (VEGF) and Erythropoietin in low oxygen conditions (hypoxia). VEGF is strongly induced at both mRNA protein level by hormones factors smooth muscle cells (VSMC) independently environment. However, role HIF-1α this induction has not been studied. We report here that levels are increased fetal calf serum quiescent VSMC. More interestingly, Angiotensin II (Ang II), thrombin, platelet-derived factor, other can also increase VSMC to substantially more elevated than hypoxic treatment. Ang located nucleus, binds response element, transcriptionally active. The mediated through production reactive species (ROS), since it be blocked ROS inhibitors, diphenyleneiodonium catalase. Finally, strong inhibited these inhibitors. These results implicate HIF-1-dependent transcriptional activity after agonist stimulation define novel hypoxia-independent mechanisms should play major remodeling.