Critical Role of Hemopexin Mediated Cytoprotection in the Pathophysiology of Sickle Cell Disease
Open Access
- 15 June 2021
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (12), 6408
- https://doi.org/10.3390/ijms22126408
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.Funding Information
- National Institutes of Health (R21NS110008, R56NS116076, NR018848)
This publication has 52 references indexed in Scilit:
- Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemiaBMC Neuroscience, 2013
- Mechanisms of neuroprotection by hemopexin: modeling the control of heme and iron homeostasis in brain neurons in inflammatory statesJournal of Neurochemistry, 2013
- A global perspective on sickle cell diseasePediatric Blood & Cancer, 2012
- Toll‐like receptor 4 contributes to poor outcome after intracerebral hemorrhageAnnals of Neurology, 2011
- Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohortBlood, 2011
- Sickle-cell diseaseThe Lancet, 2010
- DESIGN OF THE SILENT CEREBRAL INFARCT TRANSFUSION (SIT) TRIALPediatric Hematology and Oncology, 2010
- Heme Oxygenase-1 Increases Endothelial Progenitor CellsArteriosclerosis, Thrombosis, and Vascular Biology, 2009
- Heme–Hemopexin Complex Attenuates Neuronal Cell Death and Stroke DamageJournal of Cerebral Blood Flow & Metabolism, 2009
- MCD, EPR and NMR spectroscopic studies of rabbit hemopexin and its heme binding domainBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1995