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Hemopexin-Mediated Cytoprotection in Sickle Cell
Hemopexin (Hpx) is a unique internal scavenging glycoprotein that is responsible for the homeostatic maintenance of blood through the regulatory binding of free heme, which eliminates heme’s harmful pro-oxidant and pro-inflammatory potential. Sickle cell disease (SCD) is caused by mutations in the Hb subunit β (HBB) gene coding for the β-globin subunit of the Hb molecule. Specifically, in the series of hemoglobinopathies included under the umbrella term SCD, at least one of the two β-globin subunits of Hb is replaced with the abnormal β-globin hemoglobin S (HbS).
Circulating hemopexin is the primary protein responsible for the clearance of heme; therefore, it is a systemic combatant against deleterious inflammation and oxidative stress induced by the presence of free heme. This role of hemopexin is critical in hemolytic pathophysiology. In this review, we outline the current research regarding how the dynamic activity of hemopexin is implicated in sickle cell disease, which is characterized by a pathological aggregation of red blood cells and excessive hemolysis. This pathophysiology leads to symptoms such as acute kidney injury, vaso-occlusion, ischemic stroke, pain crises, and pulmonary hypertension exacerbated by the presence of free heme and hemoglobin. This review includes in vivo studies in mouse, rat, and guinea pig models of sickle cell disease, as well as studies in human samples. In summary, the current research indicates that hemopexin is likely protective against these symptoms and that rectifying depleted hemopexin in patients with sickle cell disease could improve or prevent the symptoms. The data compiled in this review suggest that further preclinical and clinical research should be conducted to uncover pathways of hemopexin in pathological states to evaluate its potential clinical function as both a biomarker and therapy for sickle cell disease and related hemoglobinopathies.
2. Heme Clearance
3. Sickle Cell Disease
4. Sickle Cell Disease and Hemolysis
The entry is from 10.3390/ijms22126408
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