Antisickling fetal hemoglobin reduces hypoxia-inducible factor-1α expression in normoxic sickle mice: microvascular implications

Chronic inflammation is a salient feature of sickle cell disease (SCD) and transgenic-knockout sickle (BERK) mice. Inflammation is implicated in the activation of hypoxia-inducible factor-1α (HIF-1α) under normoxic conditions. We hypothesize that, in SCD, inflammation coupled with nitric oxide (NO)...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2013-01, Vol.304 (1), p.H42-H50
Main Authors: Kaul, Dhananjay K, Fabry, Mary E, Suzuka, Sandra M, Zhang, Xiaoqin
Format: Article
Language:English
Subjects:
alpha-Globins - genetics
alpha-Globins - metabolism
Anemia, Sickle Cell - genetics
Anemia, Sickle Cell - metabolism
Anemia, Sickle Cell - physiopathology
Anemia, Sickle Cell - therapy
Animals
Arginine - pharmacology
Arterioles - drug effects
Arterioles - metabolism
Arterioles - physiopathology
beta-Globins - genetics
beta-Globins - metabolism
Blood Pressure
Disease Models, Animal
Down-Regulation
Endothelin-1 - blood
Fetal Hemoglobin - genetics
Fetal Hemoglobin - metabolism
Heme Oxygenase-1 - metabolism
Humans
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Inflammation - genetics
Inflammation - metabolism
Inflammation - physiopathology
Inflammation - therapy
Membrane Proteins - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microcirculation - drug effects
Nitric Oxide - metabolism
Regional Blood Flow
Vascular Biology and Microcirculation
Vascular Endothelial Growth Factor A - metabolism
Vasodilation
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Summary:Chronic inflammation is a salient feature of sickle cell disease (SCD) and transgenic-knockout sickle (BERK) mice. Inflammation is implicated in the activation of hypoxia-inducible factor-1α (HIF-1α) under normoxic conditions. We hypothesize that, in SCD, inflammation coupled with nitric oxide (NO) depletion will induce expression of HIF-1α, a transcription factor with wide-ranging effects including activation of genes for vasoactive molecules. To this end, we have examined the expression of HIF-1α in normoxic BERK mice expressing exclusively human α- and β(S)- globins, and evaluated the effect of fetal hemoglobin (HbF) in BERK mice (i.e.,
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00296.2012