Researchers Discover Enzyme Deficiency in Sickle Cell Disease that May Lead to New Therapy

Rockville, Md. (February 24, 2022)—Research published ahead of print in the journal Function suggests that expression of the enzyme superoxide dismutase 2 is decreased in endothelial cells in people with sickle cell disease.

Sickle cell disease is a genetic condition in which red blood cells are misshapen, which causes them to build up in the blood vessels. The condition can lead to episodes of severe pain and organ damage. Superoxide dismutase 2 is an enzyme that has shown to play a crucial role in blood vessel (vascular) health. A lack of the enzyme increases oxidative stress, damage at the cellular level, which can lead to vascular dysfunction.

Using human lung tissue samples and a mouse model of sickle cell disease, researchers found that the endothelial cells—cells that line the blood vessels—had lower levels of superoxide dismutase 2 expression than those without sickle cell disease. This type of deficiency leads to disruption of fibronectin processing. Fibronectin is an extracellular matrix (ECM) protein that regulates biological processes such as wound healing and tumor progression.

“This disruption of fibronectin processing consequently leads to decreased adhesion, migration and proliferation, integrin protein dysregulation, as well as an increase in permeability. Taken together, these data suggest that further investigation into therapeutic treatments targeting [Superoxide dismutase 2]-mediated changes in ECM protein assembly may be beneficial in [sickle cell disease],” the researchers wrote.

Read the full article, “Endothelial superoxide dismutase 2 is decreased in sickle cell disease and regulates fibronectin processing.” Contact APS Media Relations to schedule an interview with the research team.