Journal of Translational Medicine volume 17 , Article number: Cite this article. Metrics details. A Correction to this article was published on 16 January Introduction: Nitric oxide NO is a critical regulator of vascular homeostasis, increasing basal and flow-mediated vasodilation.
In contrast, red blood cell hemolysis releases hemoglobin into plasma, where can react with and scavenge NO. In this context, hemoglobin functions as an oxido-reductase: A nitrite-reductase and NO synthase when it deoxygenates and an NO oxidase when it is oxygenated, particularly in the setting of hemolysis.
The mechanistic linkage between hemolytic anemia and vasculopathy has been the subject of extensive study in pre-clinical animal models, in vascular studies in patients, and in large human cohort studies. Intravascular hemolysis releases cell-free hemoglobin into the plasma, which can scavenge NO and generate reactive oxygen species, impairing redox balance and leading to proliferative systemic and pulmonary vasculopathy.
Pre-clinical studies also suggest that sGC may be oxidized in sickle cell disease, and responsive to sGC activator therapy. Large screening studies of patients with sickle cell disease SCD for the presence of pulmonary hypertension PH have been performed using non-invasive Doppler-echocardiography, screening biomarkers such as N-terminal brain natriuretic peptide and right heart catheterization.
These studies have reported a high prevalence of PH in this population, a significant association of increasing pulmonary pressures with more severe hemolytic anemia, cutaneous leg ulcerations, systemic systolic hypertension and renal dysfunction, and a high prospective associated risk of death.
