Plasma hepcidin of Ethiopian highlanders with steady-state hypoxia

Lundgrin, Erika L.; Janocha, Allison J.; Koch, Carl; Gebremedhin, Amha; Rienzo, Anna Di; Alkorta‐Aranburu, Gorka; Brittenham, Gary M.; Erzurum, Serpil C.

doi:10.1182/blood-2013-03-491068

Cited by 26 publications

(31 citation statements)

References 10 publications

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“…Inhibition of erythropoietin with neutralizing antibodies, or disruption of Epo in mice, significantly reversed HIF2α-mediated repression of Hamp 78, 79 . These findings are consistent with a recent study of indigenous populations who live at high altitudes 81 . Although exposure of volunteers to high-altitude hypoxia significantly decreased levels of hepcidin and increased in erythropoietin and RBC production, 75 indigenous highlanders with stable erythropoietic iron requirements did not have reduced levels of hepcidin compared to their lowland counterparts 81 .…”

Section: Introductionsupporting

confidence: 93%

“…These findings are consistent with a recent study of indigenous populations who live at high altitudes 81 . Although exposure of volunteers to high-altitude hypoxia significantly decreased levels of hepcidin and increased in erythropoietin and RBC production, 75 indigenous highlanders with stable erythropoietic iron requirements did not have reduced levels of hepcidin compared to their lowland counterparts 81 . These findings support the concept that erythropoietin and/or erythropoiesis are involved in hypoxia-mediated suppression of HAMP .…”

Section: Introductionsupporting

confidence: 93%

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Hypoxia-Inducible Factors Link Iron Homeostasis and Erythropoiesis

2014

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Iron is required for efficient oxygen transport, and hypoxia signaling links erythropoiesis with iron homeostasis. Hypoxia induces a highly conserved signaling pathway in cells under conditions of low O2. One component of this pathway, hypoxia-inducible factor (HIF), is a transcription factor that is highly active in hypoxic cells. The first HIF target gene characterized was EPO, which encodes erythropoietin—a glycoprotein hormone that controls erythropoiesis. The past decade has led to fundamental advances in our understanding of how hypoxia regulates iron levels to support erythropoiesis and maintain systemic iron homeostasis. We review the cell-type specific effects of hypoxia and HIFs in adaptive response to changes in oxygen and iron availability, as well as potential uses of HIF modulators for patients with iron-related disorders.

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Section: Introductionsupporting

confidence: 93%

Section: Introductionsupporting

confidence: 93%

Hypoxia-Inducible Factors Link Iron Homeostasis and Erythropoiesis

2014

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“…Despite significant hypoxemia (arterial SpO 2 83 6 1%, mean 6 standard error of the mean) and exaggerated erythropoiesis, baseline hepcidin levels in CMS patients (8.8 6 3.0 ng/mL) were similar to those reported both for healthy Peruvian lowlanders at sea level 2 and healthy high-altitude populations in Ethiopia. 8 This seems likely to reflect the relatively stable, albeit elevated, erythropoietic activity in these groups, and is in keeping with the classical concept of an erythroid regulator that signals imbalance between erythropoietic drive and iron supply, rather than absolute marrow activity. 13 Venesection produced a 20% fall in hematocrit by day 5 (P , .01, paired Student t test), accompanied by a rise in plasma EPO (P , .05) and a marked fall in plasma hepcidin (P , .05).…”

supporting

confidence: 66%

“…8,9 In recent years, numerous mediators have been proposed as the link between erythropoiesis and hepcidin suppression (the so-called "erythroid regulator"). Candidates include growthdifferentiation factor 15 (GDF-15), soluble transferrin receptor (sTfR), erythropoietin (EPO), and the novel hormone erythroferrone, recently described in mice and reported to be the product of the gene Fam132b.…”

mentioning

confidence: 99%

Suppression of plasma hepcidin by venesection during steady-state hypoxia

Talbot

Smith

Lakhal‐Littleton

et al. 2016

Blood

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“…En los nativos de la altura, la situación es diferente, como ha sido demostrado en etíopes, los valores basales de hepcidina en adultos son similares o mayores que a baja altitud (21) lo que demuestra que son suficientes en hierro. Cuando se hace sangría en la altura, los niveles de hepcidina se reducen para aumentar la disponibilidad de hierro producida por la extracción de sangre (22) .…”

Section: Gonzales Gf Et Alunclassified

Necesidades de investigación para el diagnóstico de anemia en poblaciones de altura

Gonzáles

Fano

2017

Rev Peru Med Exp Salud Publica

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RESUMENTanto la deficiencia como la sobrecarga de hierro son situaciones que ponen en riesgo la salud y la vida de las personas, por lo que es importante mantener su homeostasis. Como la hemoglobina contiene 70% del hierro del organismo, la OMS recomienda su medición para determinar la prevalencia de anemia por deficiencia de hierro (ID), a pesar que ellos mismos reconocen que la anemia no es específica de ID. Como la hemoglobina aumenta con la altitud de residencia, la OMS recomienda corregir el punto de corte para definir anemia en la altura. Una objeción a esta corrección es que el aumento de la hemoglobina en la altura no es universal ni aumenta de manera lineal. Además, las poblaciones de mayor antigüedad generacional tienen menos hemoglobina que las más recientes. En infantes, niños, gestantes y adultos, la prevalencia de anemia usando hemoglobina corregida es 3-5 veces mayor que usando marcadores del estatus de hierro. Los programas estatales buscan combatir la anemia mediante la suplementación de hierro; no obstante, resultan ineficaces, especialmente en las poblaciones de altura. Entonces, ¿hay deficiencia de hierro en la altura? Los niveles de hepcidina sérica, hormona que regula la disponibilidad de hierro, son similares a los de nivel del mar indicando que en la altura no hay deficiencia de hierro. Un problema adicional al corregir la hemoglobina por la altura, es que las prevalencias de eritrocitosis disminuyen. En conclusión, la corrección del punto de corte de la hemoglobina en la altura para determinar deficiencia de hierro es inadecuada. Palabras clave: Anemia, Deficiencia de hierro, Factor de corrección, Ferritinas (fuente: DeCS BIREME). DIAGNOSIS OF ANEMIA IN POPULATIONS AT HIGH ALTITUDES ABSTRACTIron deficiency and overload are risk factors for numerous poor health outcomes, and thus the maintenance of iron homeostasis is vital. Considering that hemoglobin contains 70% of the total iron in the body, the World Health Organization (WHO) recommends the measurement of iron levels to calculate the rate of iron deficiency anemia (IDA), although WHO recognizes that IDA is not the only cause of anemia. As hemoglobin increases with altitude, WHO recommends correcting the cut-off point to define anemia at high altitudes. An objection to this correction is that the increase in hemoglobin at high altitudes is not universal and is not linear. In addition, individuals in older age groups have lower hemoglobin levels than those in younger age groups. In infants, children, pregnant women, and adults, the prevalence of anemia using corrected hemoglobin is 3-5 times higher than that using markers of iron status. State programs seek to control anemia by means of iron supplementation. However, these programs are ineffective, particularly for high-altitude populations. Therefore, the occurrence of iron deficiency at high altitudes is controversial. The serum levels of the hormone hepcidin, which regulates iron availability, are similar in individuals at high altitudes to those of individuals at sea level, indicat...

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Plasma hepcidin of Ethiopian highlanders with steady-state hypoxia

Cited by 26 publications

References 10 publications

Hypoxia-Inducible Factors Link Iron Homeostasis and Erythropoiesis

Hypoxia-Inducible Factors Link Iron Homeostasis and Erythropoiesis

Suppression of plasma hepcidin by venesection during steady-state hypoxia

Necesidades de investigación para el diagnóstico de anemia en poblaciones de altura

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