Therapeutic potential of haptoglobin in a murine model of sickle cell anemia.

Abstract

Chronic hemolytic anemia found in patients with sickle cell disease promotes an excess of free extracellular and intravascular hemoglobin, triggering a series of deleterious effects such as endothelial dysfunction, oxidative stress, and alterations in vascular tone, which lead to clinical complications. In this work, we evaluated the induced expression of haptoglobin in hepatocytes in vivo, the organism's first line of defense to control the presence of free Hb in circulation, which becomes saturated in conditions of chronic hemolysis, such as sickle cell disease. Through gene therapy applied in a murine model of sickle cell anemia, we aimed to investigate whether this approach could interfere with disease progression and promote an improvement in the animals' pathophysiological condition. The application of this treatment in the sickle cell anemia animal model resulted in significant therapeutic effects, including improvement of hematological parameters, reduction of the compensatory erythropoietic response, and attenuation of clinical signs such as splenomegaly. These results indicate that haptoglobin may act indirectly in the prevention of hemolysis, suggesting a new therapeutic approach.