Heme Oxygenase Pathways in Sickle Cell Disease and Inflammation

Dear Colleagues,

Sickle cell disease (SCD) is a devastating hemolytic disease marked by recurring bouts of painful vaso-occlusion, leading to tissue damage from ischemia/reperfusion pathophysiology. Central to this process are oxidative stress, endothelial cell activation, and inflammation. Reactive oxygen species (ROS) production, notably spurred by heme iron, fuels vascular inflammation by activating redox-sensitive transcription factors including NF-κB and AP-1 in endothelial cells. The heightened hemolysis in SCD exposes endothelial cells to elevated ROS levels, catalyzed by iron. Heme, a hydrophobic iron-containing compound, escalates cellular vulnerability to oxidative injury by intercalating rapidly into cell membranes. The vasculature's defense mechanism against the released heme involves inducing four protective genes: haptoglobin, hemopexin, heme oxygenase 1 (HO-1), and ferritin. Haptoglobin and hemopexin scavenge free hemoglobin and heme, respectively, in the plasma, but are rapidly depleted in SCD. HO-1, a pivotal enzyme in heme catabolism, breaks down heme into biliverdin, free iron, and carbon monoxide (CO), exerting crucial cytoprotective effects. The induction of HO-1 coincides with apoferritin induction, which sequesters nonreactive Fe³⁺ within ferritin complexes. Studies have demonstrated HO-1's efficacy in shielding tissues from various insults, including ischemia/reperfusion injury, oxidative stress, and inflammation. Conversely, deficiencies in HO-1 render both humans and mice more susceptible to oxidant-mediated harm. Thus, HO-1 has emerged as a significant anti-inflammatory player, particularly in the context of SCD.

Potential topics include, but are not limited to, the following:

• Malaria and other hemolytic diseases;
• Antioxidant properties;
• Antioxidant mechanisms of action;
• Antioxidant and anti-inflammatory action.

Prof. Dr. John Belcher
Prof. Dr. Gregory Vercellotti
Guest Editors

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• heme oxygenase
• inflammation
• sickle cell disease
• hemolysis