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
| Autor: | Matthew T. Rondina, Ke-xia Chai, Zhanquan Li, Hui Geng, Linhua Ji, Tana Wuren, Juan Su, Xiaojing Ma, Ri Li Ge, Yingzhong Yang, Sen Cui, Zhen-Zhong Bai |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Scientific Articles medicine.medical_specialty Physiology Angiogenesis Polycythemia Altitude Sickness Pathogenesis Hemoglobins Bone Marrow Internal medicine Basic Helix-Loop-Helix Transcription Factors medicine Humans RNA Messenger Erythropoietin Neovascularization Pathologic business.industry Altitude Public Health Environmental and Occupational Health General Medicine Middle Aged medicine.disease Erythropoietin receptor Endocrinology medicine.anatomical_structure Chronic mountain sickness Hypoxia-inducible factors Case-Control Studies Chronic Disease Microvessels Immunology Erythropoiesis Bone marrow business Signal Transduction medicine.drug |
| Zdroj: | High Altitude Medicine & Biology. 16:318-330 |
| ISSN: | 1557-8682 1527-0297 3000-4500 |
| DOI: | 10.1089/ham.2015.0015 |
| Popis: | 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.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.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. |
| Databáze: | OpenAIRE |
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