Pulmonary hypertension is characterized by pulmonary endothelial dysfunction. Previous work showed that systemic artery endothelial cells express hemoglobin α to control nitric oxide diffusion, but the role of this system in the pulmonary circulation has not been evaluated.
We hypothesize that up-regulation of hemoglobin α in pulmonary endothelial cells contributes to nitric oxide depletion and pulmonary vascular dysfunction in pulmonary hypertension.
Co-cultures of human pulmonary microvascular endothelial cells and distal pulmonary arterial vascular smooth muscle cells, lung tissue from control and pulmonary hypertensive lungs, and a mouse model of chronic hypoxia-induced pulmonary hypertension were used. Immunohistochemical, immunoblot analyses, spectrophotometry, and blood vessel myography experiments were performed in this study.
We find increased expression of hemoglobin α in pulmonary endothelium from humans and mice with pulmonary hypertension compared to controls. In addition, we show up-regulation of hemoglobin α in human pulmonary endothelial cells co-cultured with pulmonary artery smooth muscle cells in hypoxia. We treated pulmonary endothelial cells with a hemoglobin α mimetic peptide that disrupts the association of hemoglobin α with endothelial nitric oxide synthase, and found that cells treated with the peptide exhibited increased nitric oxide signaling compared to a scrambled peptide. Myography experiments using pulmonary arteries from hypoxic mice show that the hemoglobin α mimetic peptide enhanced vasodilation in response to acetylcholine.
Our findings reveal that endothelial hemoglobin α functions as an endogenous scavenger of nitric oxide in the pulmonary endothelium. Targeting this pathway may offer a novel therapeutic target to increase endogenous levels of nitric oxide in pulmonary hypertension.
This research output has an Altmetric Attention Score of 8. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 October 2023.
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Altmetric has tracked 34,089,221 research outputs across all sources so far. Compared to these this one has done well and is in the 81st percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,365 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.9. This one has done well, scoring higher than 83% of its peers.
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