Increased transferrin protects from thrombosis in Chuvash erythrocytosis.

ABSTRACT: Von Hippel-Lindau protein (VHL) is essential to hypoxic regulation of cellular processes. VHL promotes proteolytic clearance of hypoxia-inducible transcription factors (HIFs) that have been modified by oxygen-dependent HIF-prolyl hydroxylases. A homozygous loss-of-function VHL^R200W mutation causes Chuvash erythrocytosis, a congenital disorder caused by augmented hypoxia-sensing. Homozygous VHL^R200W results in accumulation of HIFs that increase transcription of the erythropoietin gene and raise hematocrit. Phlebotomies reduce hematocrit and hyperviscosity symptoms. However, the major cause of morbidity and mortality in Chuvash erythrocytosis is thrombosis. Phlebotomies cause iron deficiency, which may further elevate HIF activity and transferrin, the HIF-regulated plas

SUBMITTER: Shah BN 

PROVIDER: S-EPMC10529798 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature