Abstract
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.
Highlights
Heme ClearanceHemopexin (Hpx) works with haptoglobin (Hp) to simultaneously combat downstream pro-oxidant and pro-inflammatory damage mediated by the presence of free heme and its predecessor, hemoglobin (Hb)
High-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol (TC) levels were lower in patients with sickle cell disease (SCD) than in AA volunteers [33,51]; there is evidence that increased hemolysis may be positively correlated with hypocholesterolemia
There is ample evidence that Hpx is a unique, multitasking protein that plays a significant role in heme-mediated protection against microvascular stasis, vaso-occlusion, and lipid oxidation, in patients with SCD
Summary
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 [1]. Via receptor-mediated signal transduction and direct Fenton oxidation, heme and Hb, as well as their oxidized respective counterparts hemin and metHb, induce cell damage and hemodynamic conditions that are deleterious to the prognosis of several pathologies [7]. It is well documented that heme is a potent inducer of heme oxygenase-1 (HO1) involving the Nrf pathway, and the activation of such pathway leads to the increased expression of various other proteins that can mitigate heme-related toxicity. This protection is critical in pathologies that induce increased hemolytic conditions, such as sickle cell disease (SCD)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
