GPx3 deficiency exacerbates maladaptive right ventricular remodeling in experimental pulmonary artery banding

Autor: Taylor A. Covington, Patrick M. Pilz, Ryan M. Mulhern, Soeun Ngoy, Alex Loscalzo, Jing Liu, Sudeshna Fisch, Jana Grune
Rok vydání: 2023
Předmět:
Zdroj: American Journal of Physiology-Lung Cellular and Molecular Physiology. 324:L550-L556
ISSN: 1522-1504
1040-0605
DOI: 10.1152/ajplung.00379.2022
Popis: 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 antioxidative capacity, like glutathione peroxidase 3 (GPx3), in RV pathogenesis is currently unknown. Here, we use a murine model of pulmonary artery banding (PAB) to study the role of GPx3 in isolated RV pathology. Compared with wild-type (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 with WT controls. Adverse RV remodeling was enhanced in GPx3-deficient PAB animals, evidenced by increased RV expression levels of connective tissue growth factor ( CTGF), transforming growth factor-β ( TGF-β), and atrial natriuretic peptide ( ANP). In summary, GPx3 deficiency exacerbates maladaptive RV remodeling and causes signs of RV dysfunction.
Databáze: OpenAIRE