Direct soluble guanylate cyclase activation improves vascular function in a mouse model of sickle cell disease

Sickle cell disease (SCD) is caused by a point mutation in the hemoglobin (Hb) β gene, which generates hemoglobin S (HbS). A less soluble tetramer that undergoes polymerization. Endothelial dysfunction caused by chronic intravascular hemolysis is a hallmark of SCD affecting multiple organs, including the lung. A common complication of SCD is pulmonary arterial hypertension (PAH) which is associated with early mortality. In the present study, we use an established animal model of SCD to investigate novel soluble guanylate cyclase (sGC) targeting in the pathobiology of global vascular dysfunction. \ud The transgenic BERK sickle mouse develops significant vascular dysfunction with age. Novel targeting of smooth muscle cell sGC represents a novel therapeutic approach for global vascular dysfunction