Loss of alpha-globin genes in human subjects is associated with improved nitric oxide-mediated vascular perfusion - PubMed (original) (raw)

. 2021 Mar 1;96(3):277-281.

doi: 10.1002/ajh.26058. Epub 2020 Dec 12.

Payal Shah 2, Silvie Suriany 3, Honglei Liu 3, Wanwara Thuptimdang 4, John Sunwoo 4, Patjanaporn Chalacheva 4, Saranya Veluswamy 1, Roberta Kato 5, John C Wood 3, Jon A Detterich 3, Michael C K Khoo 4, Thomas D Coates 1

Affiliations

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

Christopher C Denton et al. Am J Hematol. 2021.

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.

© 2020 Wiley Periodicals LLC.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflict of interest.

J.C.W. has consultancy with BluebirdBio, Celgene, WorldcareClinical, BiomedInformatics, and Imago Biosciences, and receives research funding from Philips Medical Systems; T.D.C. has consultancy and honoraria with Celgene, Chiesi Pharma, Agios Pharmaceuticals, and Sangamo, and holds membership on advisory committees for Celgene and Sangamo.

Figures

FIGURE 1

FIGURE 1

Multivariate analysis of flow-mediated dilation (FMD) vs α-trait and age. A, Least squares means of FMD in control and α-trait. FMD is significantly higher in α-trait (P = .036) after controlling for age. B, Multivariate regression plot. Regression lines are shown with control indicated by red points and α-trait indicated in blue. Model R2 = 0.22 (F2,24 = 3.407, P = .050)

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