Loss of alpha-globin genes in human subjects is associated with improved nitric oxide-mediated vascular perfusion.

Abstract

Alpha thalassemia is a hemoglobinopathy due to decreased production of the α-globin protein from loss of up to four α-globin genes, with one or two missing in the trait phenotype. Individuals with sickle cell disease who co-inherit the loss of one or two α-globin genes have been known to have reduced risk of morbid outcomes, but the underlying mechanism is unknown. While α-globin gene deletions affect sickle red cell deformability, the α-globin genes and protein are also present in the endothelial wall of human arterioles and participate in nitric oxide scavenging during vasoconstriction. Decreased production of α-globin due to α-thalassemia trait may thereby limit nitric oxide scavenging and promote vasodilation. To evaluate this potential mechanism, we performed flow-mediated dilation and microvascular post-occlusive reactive hyperemia in 27 human subjects (15 missing one or two α-globin genes and 12 healthy controls). Flow-mediated dilation was significantly higher in subjects with α-trait after controlling for age (P = .0357), but microvascular perfusion was not different between groups. As none of the subjects had anemia or hemolysis, the improvement in vascular function could be attributed to the difference in α-globin gene status. This may explain the beneficial effect of α-globin gene loss in sickle cell disease and suggests that α-globin gene status may play a role in other vascular diseases.

• Authors: Christopher C Denton, Payal Shah, Silvie Suriany, Honglei Liu, Wanwara Thuptimdang, John Sunwoo, Patjanaporn Chalacheva, Saranya Veluswamy, Roberta Kato, John C Wood, Jon A Detterich, Michael C K Khoo, Thomas D Coates
• Journal: American journal of hematology (Am J Hematol) Vol. 96 Issue 3 Pg. 277-281 (03 01 2021) ISSN: 1096-8652 [Electronic] United States
• PMID: 33247606 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Wiley Periodicals LLC.

Chemical References

• alpha-Globins
• Nitric Oxide

Topics

• Adolescent
• Adult
• Anthropometry
• Blood Pressure
• Brachial Artery (pathology, physiopathology)
• Ethnicity (genetics)
• Female
• Genotype
• Hemorheology
• Humans
• Hyperemia (genetics, physiopathology)
• Laser-Doppler Flowmetry
• Male
• Microcirculation (physiology)
• Middle Aged
• Nitric Oxide (physiology)
• Vasodilation (physiology)
• Young Adult
• alpha-Globins (deficiency, genetics)
• alpha-Thalassemia (genetics, physiopathology)