GPx3 deficiency exacerbates maladaptive RV remodeling in experimental pulmonary artery banding.

Abstract

The stressed right ventricle (RV) is particularly susceptible to producing and accumulating reactive oxygen species, leading to extracellular matrix deposition and secretion of natriuretic peptides. The role of specific enzymes with anti-oxidative capacity, like Glutathione peroxidase 3 (GPx3), in RV pathogenesis is currently unknown. Here, we employ a murine model of pulmonary artery banding (PAB) to study the role of GPx3 in isolated RV pathology. Compared to WT mice undergoing PAB surgery, GPx3-deficient PAB mice presented with higher RV systolic pressure and higher LV eccentricity indices. PAB-induced changes in Fulton's Index, RV free wall thickness, and RV fractional area change were more pronounced in GPx3-deficient mice compared to WT controls. Adverse RV remodeling was enhanced in GPx3-deficient PAB animals, evidenced by increased RV expression levels of CTGF, TGF-b and ANP. In summary, GPx3 deficiency exacerbates maladaptive RV remodeling and causes signs of RV dysfunction.