Hypoxia-inducible factor as a therapeutic target for cardioprotection.

摘要: Hypoxia inducible factor (HIF) is an oxygen-sensitive transcription that enables aerobic organisms to adapt hypoxia. This achieved through the transcriptional activation of up 200 genes, many which are critical cell survival. Under conditions normoxia, hydroxylation HIF by prolyl hydroxylase domain-containing (PHD) enzymes targets it for polyubiquitination and proteosomal degradation von Hippel-Lindau protein (VHL). However, under hypoxic conditions, PHD activity inhibited, thereby allowing accumulate translocate nucleus, where binds hypoxia-responsive element sequences target gene promoters. Experimental studies suggest may act as a mediator ischemic preconditioning, genetic or pharmacological stabilization normoxic protect heart against detrimental effects acute ischemia-reperfusion injury. The mechanisms underlying cardioprotective effect unclear, but be attributed genes associated with cardioprotection such erythropoietin, heme oxygenase-1, nitric oxide synthase due reprogramming metabolism. In this review article, we highlight role in mediating both adaptive pathological processes heart, well focusing on therapeutic potential HIF-signaling pathway cardioprotection.