Year: 2025
Type: article
Abstract: Sickle cell disease (SCD) is a complex hematological disorder marked by chronic hemolysis, inflammation, and recurrent vaso-occlusive crises. A critical but often underemphasized factor contributing to the pathophysiology of SCD is the disruption of nitric oxide (NO) signaling due to excessive interactions with hemoglobin. The release of free hemoglobin into the plasma during hemolysis rapidly scavenges NO, impairing its vasodilatory and antiinflammatory functions. This biochemical imbalance contributes significantly to endothelial dysfunction and vascular complications observed in SCD patients. The bioavailability of NO is further diminished by increased oxidative stress and the release of arginase from lysed erythrocytes, which depletes L-arginine—an essential substrate for endothelial NO synthesis. The resulting NO-deficient environment promotes vasoconstriction, leukocyte adhesion, and platelet activation, escalating the risk of vascular occlusion and organ damage. These processes not only exacerbate the frequency and severity of vaso-occlusive episodes but also contribute to the long-term morbidity associated with SCD, such as pulmonary hypertension and leg ulcers.
Source: Journal of Bio Innovation
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4410332503