Increased blood reactive oxygen species and hepcidin in obstructive sleep apnea precludes expected erythrocytosis
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
Grant support
R01 DK065029
NIDDK NIH HHS - United States
1R01DK126680
NIDDK NIH HHS - United States
5T32DK007115
NIDDK NIH HHS - United States
2T32HL007576-31
NHLBI NIH HHS - United States
PubMed
37350302
DOI
10.1002/ajh.26992
Knihovny.cz E-resources
- MeSH
- Hepcidins MeSH
- Hypoxia MeSH
- Humans MeSH
- Sleep Apnea, Obstructive * complications MeSH
- Polycythemia * etiology MeSH
- Reactive Oxygen Species MeSH
- Inflammation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Names of Substances
- Hepcidins MeSH
- Reactive Oxygen Species MeSH
Obstructive sleep apnea (OSA) causes intermittent hypoxia during sleep. Hypoxia predictably initiates an increase in the blood hemoglobin concentration (Hb); yet in our analysis of 527 patients with OSA, >98% did not have an elevated Hb. To understand why patients with OSA do not develop secondary erythrocytosis due to intermittent hypoxia, we first hypothesized that erythrocytosis occurs in these patients, but is masked by a concomitant increase in plasma volume. However, we excluded that explanation by finding that the red cell mass was normal (measured by radionuclide labeling of erythrocytes and carbon monoxide inhalation). We next studied 45 patients with OSA before and after applying continuous positive airway pressure (CPAP). We found accelerated erythropoiesis in these patients (increased erythropoietin and reticulocytosis), but it was offset by neocytolysis (lysis of erythrocytes newly generated in hypoxia upon return to normoxia). Parameters of neocytolysis included increased reactive oxygen species from expanded reticulocytes' mitochondria. The antioxidant catalase was also downregulated in these cells from hypoxia-stimulated microRNA-21. In addition, inflammation-induced hepcidin limited iron availability for erythropoiesis. After CPAP, some of these intermediaries diminished but Hb did not change. We conclude that in OSA, the absence of significant increase in red cell mass is integral to the pathogenesis, and results from hemolysis via neocytolysis combined with inflammation-mediated suppression of erythropoiesis.
Centre for Physical Activity Research Copenhagen Denmark
Department of Biology Palacky University Olomouc Olomouc Czech Republic
Department of Neonatology University of Utah Salt Lake City Utah USA
Division of Hematology University of Utah Salt Lake City Utah USA
Division of Pulmonary and Critical Care Medicine University of Utah Salt Lake City Utah USA
Pathology and Laboratory Medicine UCLA Los Angeles California USA
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