Sickle Trait and Alpha Thalassemia Increase NOS-Dependent Vasodilation of Human Arteries Through Disruption of Endothelial Hemoglobin-eNOS Interactions
Authors' conclusion
Alpha and beta globin subunits of hemoglobin interact with eNOS to restrict NO signaling in human resistance arteries. Malaria-protective genetic variants that alter the expression of alpha globin or the structure of beta globin are associated with increased NOS-dependent vasodilation.
Study context
- Population
- Human resistance arteries from donors; population study for alpha globin gene deletion and BP
- Comparison
- Sickle trait and alpha globin gene deletion vs no variant; mimetic peptides disrupting hemoglobin-eNOS interactions
- Outcome
- NOS-dependent vasodilation of human arteries and the eNOS-hemoglobin complex
Methodological detailshuman resistance arteries, multiphoton imaging, coimmunoprecipitation, molecular modeling and simulation, pressure myography, population study
- Human resistance arteries
- Multiphoton imaging
- Coimmunoprecipitation
- Molecular modeling and simulation
- Pressure myography
- Population study
Main finding
As reported in the abstract
- Alpha and beta globin transcripts detected in the endothelial layer of the artery wall
- Imaging colocalized alpha and beta globin proteins with endothelial NOS (eNOS) at myoendothelial junctions
- Immunoprecipitation: alpha globin and beta globin form a complex with eNOS and cytochrome b5 reductase
- Modeling predicted negatively charged glutamic acids at beta globin positions 6 and 7 interact with positively charged arginines at eNOS positions 97 and 98
- Sickle trait arteries: increased NOS-dependent vasodilation
- Alpha globin gene deletions: decreased arterial alpha globin expression, increased NOS-dependent vasodilation, lower BP
- Mimetic peptides targeting hemoglobin-eNOS interactions recapitulated the effects of these genetic variants on human arterial vasoreactivity
Original publication
Sickle Trait and Alpha Thalassemia Increase NOS-Dependent Vasodilation of Human Arteries Through Disruption of Endothelial Hemoglobin-eNOS Interactions. Circulation. Published 5 December 2024. doi:10.
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