Cellular Adhesion and the Endothelium
P-selectin on endothelial cell surfaces is central to impaired microvascular blood flow in sickle cell disease (SCD). Restoration of blood flow is expected to provide therapeutic benefit for SCD patients,…
HEMATOLOGY
Alterations of the Arginine Metabolome in Sickle Cell Disease
Low global arginine bioavailability (GAB) is associated with numerous complications of SCD including early mortality. Mechanisms of arginine dysregulation involve a complex paradigm of excess activity of the arginine-consuming enzyme…
The Role of Adenosine Signaling in Sickle Cell Therapeutics
Data suggest a role for adenosine signaling in the pathogenesis of sickle cell disease (SCD). Signaling through the adenosine A 2A receptor (A 2A R) has demonstrated beneficial effects. Activation…
Inflammatory Mediators of Endothelial Injury in Sickle Cell Disease
Inflammation plays a critical role in the complex pathophysiology of sickle cell disease and drives both the acute and chronic processes leading to vascular injury. Mediators of inflammation, such as…
Does Erythropoietin Have a Role in the Treatment of β-Hemoglobinopathies?
This review presents the indications and contraindications (pros and cons) for the potential use of erythropoietin (Epo) as a treatment in β-thalassemia and sickle cell anemia (SCA). Its high cost…
Targeted Fetal Hemoglobin Induction for Treatment of Beta Hemoglobinopathies
Fetal globin (gamma globin; HBG) is normally expressed during fetal life and prevents the clinical manifestations of beta hemoglobinopathies before birth. HBG genes are normally integrated in hematopoietic stem cells…
Therapeutic Strategies to Alter the Oxygen Affinity of Sickle Hemoglobin
The pathophysiology of sickle cell disease involves the polymerization of sickle hemoglobin in its T state, which develops under low oxygen saturation. One therapeutic strategy is to develop pharmacologic agents…
Gene Therapy for Hemoglobinopathies
After nearly two decades of struggle, gene therapy for hemoglobinopathies using vectors carrying β or γ-globin gene has finally reached the clinical doorsteps. This was made possible by advances made…
Ischemia-reperfusion Injury in Sickle Cell Anemia
Ischemia-reperfusion (I/R) physiology, also called reperfusion injury, instigates vascular and tissue injury in human disease states. This review describes why sickle cell anemia should be conceptualized in this fashion and…
Hemoglobin S Polymerization and Red Cell Membrane Changes
Different pathways lead from the simple point mutation in hemoglobin to the membrane changes that characterize the altered interaction of the sickle red blood cell with its environment, including endothelial…
