Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor Improves Leukocyte Energy Metabolism in Hereditary Hemorrhagic Telangiectasia.

ABSTRACT: The interplay between hypoxia-inducible factors (HIFs) and transforming growth factor beta (TGF-β) is critical for both inflammation and angiogenesis. In hereditary hemorrhagic telangiectasia (HHT), we have previously observed that impairment of the TGF-β pathway is associated with downregulation of HIF-1α. HIF-1α accumulation is mandatory in situations of altered energy demand, such as during infection or hypoxia, by adjusting cell metabolism. Leukocytes undergo a HIF-1α-dependent switch from aerobic mitochondrial respiration to anaerobic glycolysis (glycolytic switch) after stimulation and during differentiation. We postulate that the decreased HIF-1α accumulation in HHT leads to a clinically observed immunodeficiency in these patients. Examination of HIF-1α and its target genes in fresh

SUBMITTER: Schild Y 

PROVIDER: S-EPMC10456096 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature