title: The Local HIF-2α/EPO Pathway in the Bone Marrow is Associated with Excessive Erythrocytosis and the Increase in Bone Marrow Microvessel Density in Chronic Mountain Sickness.
abstract: OBJECTIVE
  Chronic mountain sickness (CMS) is characterized by excessive erythrocytosis, and angiogenesis may be involved in the pathogenesis of this disease. The bone marrow niche is the primary site of erythropoiesis and angiogenesis. This study was aimed at investigating the associations of the levels of hypoxia-inducible factors (HIFs), erythropoietin (EPO), and erythropoietin receptor (EPOR), as well as microvessel density (MVD) in the bone marrow with CMS.
  
  
  RESULTS
  A total of 34 patients with CMS and 30 control subjects residing in areas at altitudes of 3000-4500 m were recruited for this study. The mRNA and protein expression of HIF-2α and EPO in the bone marrow cells was significantly higher in the CMS patients than in the controls. Moreover, changes in HIF-2α expression in CMS patients were significantly correlated with EPO and hemoglobin levels. In contrast, the expression of mRNA and protein expression of HIF-1α and EPOR did not differ significantly between the CMS and control patients. Increased MVD was observed in the bone marrow of the patients with CMS and it was significantly correlated with hemoglobin.
  
  
  CONCLUSIONS
  Bone marrow cells of CMS patients may show enhanced activity of the HIF-2α/EPO pathway, and EPO may regulate the erythropoiesis and vasculogenesis through autocrine or/and paracrine mechanisms in the bone marrow niche. The increased MVD in the bone marrow of CMS patients appears to be involved in the pathogenesis of this disease.
authors.affiliation: 1 Research Center for High Altitude Medicine, Qinghai University , Xining, China .|2 Department of Hematology, Qinghai University Affiliated Hospital , Xining, China .
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.affiliation: 1 Research Center for High Altitude Medicine, Qinghai University , Xining, China .|2 Department of Hematology, Qinghai University Affiliated Hospital , Xining, China .
authors.forename: Zhanquan
authors.initials: Z
authors.lastname: Li
authors.affiliation: 1 Research Center for High Altitude Medicine, Qinghai University , Xining, China .|2 Department of Hematology, Qinghai University Affiliated Hospital , Xining, China .
authors.forename: Sen
authors.initials: S
authors.lastname: Cui
authors.affiliation: 1 Research Center for High Altitude Medicine, Qinghai University , Xining, China .|2 Department of Hematology, Qinghai University Affiliated Hospital , Xining, China .
authors.forename: Linhua
authors.initials: L
authors.lastname: Ji
authors.affiliation: 1 Research Center for High Altitude Medicine, Qinghai University , Xining, China .|2 Department of Hematology, Qinghai University Affiliated Hospital , Xining, China .
authors.forename: Hui
authors.initials: H
authors.lastname: Geng
authors.affiliation: 1 Research Center for High Altitude Medicine, Qinghai University , Xining, China .|2 Department of Hematology, Qinghai University Affiliated Hospital , Xining, China .
authors.forename: Kexia
authors.initials: K
authors.lastname: Chai
authors.affiliation: 1 Research Center for High Altitude Medicine, Qinghai University , Xining, China .|2 Department of Hematology, Qinghai University Affiliated Hospital , Xining, China .
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Ma
authors.affiliation: 1 Research Center for High Altitude Medicine, Qinghai University , Xining, China .
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Bai
authors.affiliation: 1 Research Center for High Altitude Medicine, Qinghai University , Xining, China .
authors.forename: Yingzhong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 1 Research Center for High Altitude Medicine, Qinghai University , Xining, China .
authors.forename: Tana
authors.initials: T
authors.lastname: Wuren
authors.affiliation: 1 Research Center for High Altitude Medicine, Qinghai University , Xining, China .
authors.forename: Ri-Li
authors.initials: RL
authors.lastname: Ge
authors.affiliation: 3 Division of General Internal Medicine and University Healthcare Thrombosis Service, Department of Internal Medicine, University of Utah Health Sciences Center , Salt Lake City, Utah.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Rondina
mesh_terms: D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000097:blood* / Q000150:complications; D051792:Basic Helix-Loop-Helix Proteins / Q000097:blood*; D001853:Bone Marrow / Q000098:blood supply / Q000378:metabolism*; D016022:Case-Control Studies; D002908:Chronic Disease; D004921:Erythropoietin / Q000097:blood*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011086:Polycythemia / Q000097:blood* / Q000209:etiology; D012333:RNA, Messenger / Q000097:blood; D015398:Signal Transduction; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004921:Erythropoietin; D006454:Hemoglobins; D012333:RNA, Messenger; D000099162:Endothelial PAS Domain-Containing Protein 1
keywords: bone marrow cells; chronic; erythropoietin; hypoxia-inducible factors; microvessel density; mountain sickness