Hypoxia-inducible factor as an angiogenic master switch.

摘要: Hypoxia-inducible factors (HIFs) regulate the transcription of genes that mediate response to hypoxia. HIFs are constantly expressed and degraded under normoxia, but stabilized have been widely studied in physiological pathological conditions shown contribute pathogenesis various vascular diseases. In clinical settings, HIF pathway has for its role inhibiting carcinogenesis. might also play a protective pathology ischemic Clinical trials therapeutic angiogenesis after administration single growth factor yielded unsatisfactory or controversial results, possibly because coordinated activity different HIF-induced is necessary induce mature vessel formation. Thus, manipulation simultaneously spectrum angiogenic offers superior strategy angiogenesis. Because HIF-2α plays an essential remodeling, promising approach treatment diseases caused by arterial obstruction, where insufficient development collateral vessels impedes effective therapy. Eukaryotic initiation 3 subunit e (eIF3e)/INT6 interacts specifically with induces proteasome inhibitor-sensitive degradation HIF-2α, independent hypoxia von Hippel-Lindau protein. Treatment eIF3e/INT6 siRNA stabilizes even normoxic expression several factors, at levels sufficient produce functional arteries veins vivo. We demonstrated limbs cold-injured brains reduces damage animal models. This review summarizes current understanding relationship between discuss novel oxygen-independent regulatory proteins bind HIF-α implications new method using stabilizers.