A Moonlighting Job for alpha-Globin in Blood Vessels.
Prabhodh AbbineniSrishti BaidMitchell J WeissPublished in: Blood (2024)
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.
Keyphrases
- nitric oxide synthase
- endothelial cells
- copy number
- nitric oxide
- genome wide
- blood pressure
- red blood cell
- blood flow
- african american
- pulmonary hypertension
- electron transfer
- mitochondrial dna
- hydrogen peroxide
- case control
- heart rate
- dna methylation
- poor prognosis
- computed tomography
- type diabetes
- hypertensive patients
- gene expression
- magnetic resonance
- small molecule
- atrial fibrillation
- magnetic resonance imaging
- pulmonary artery
- genome wide identification
- high throughput
- pulmonary arterial hypertension
- vascular endothelial growth factor
- genome wide analysis
- single cell
- insulin resistance
- blood glucose