Red blood cells (RBC) express high levels of hemoglobin A tetramer (HbA, 22) to facilitate oxygen (O2) transport. Hemoglobin and related proteins are also expressed at lower levels in other tissues across the animal kingdom. Physiological functions for most non-erythroid globins likely derive from their ability to catalyze reduction-oxidation (redox) reactions via electron transfer through heme-associated iron. An interesting example is illustrated by the recent discovery that -globin without -globin is expressed in some arteriolar endothelial cells (ECs). -Globin binds EC nitric oxide synthase (eNOS) and degrades its enzymatic product nitric oxide (NO), a potent vasodilator. Thus, depletion of -globin in ECs or inhibition of its association with eNOS causes arteriolar relaxation and lowering of blood pressure in mice. Some of these findings have been replicated in isolated human blood vessels and genetic studies are tractable in populations where -thalassemia alleles are prevalent. Two small studies identified associations between loss of -genes in humans and NO-regulated vascular responses elicited by local hypoxia-induced blood flow or thermal stimulation. In a few larger population-based studies, no associations were detected between loss of -globin genes and blood pressure, ischemic stroke or pulmonary hypertension. In contrast, a significant positive association between -globin gene copy number and kidney disease was detected in an African American cohort. Further studies are required to define comprehensively the expression of -globin and related globin proteins in different vascular beds and ascertain their overall impact on normal and pathological vascular physiology.
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Review Article|
June 7, 2024
A Moonlighting Job for alpha-Globin in Blood Vessels
Prabhodh Abbineni,
Prabhodh Abbineni
Loyola University Chicago, Chicago, Illinois, United States
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Srishti Baid,
Srishti Baid
University of Michigan Life Sciences Institute, Ann Arbor, Michigan, United States
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Mitchell J. Weiss
St. Jude Children's Research Hospital, Memphis, Tennessee, United States
* Corresponding Author; email: mitch.weiss@stjude.org
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Blood blood.2023022192.
Article history
Submitted:
March 11, 2024
Revision Received:
May 8, 2024
Accepted:
May 28, 2024
Citation
Prabhodh Abbineni, Srishti Baid, Mitchell J. Weiss; A Moonlighting Job for alpha-Globin in Blood Vessels. Blood 2024; blood.2023022192. doi: https://doi.org/10.1182/blood.2023022192
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