Covington Taylor A, Pilz Patrick M, Mulhern Ryan M, Ngoy Soeun, Loscalzo Alex, Liu Jing, Fisch Sudeshna, Grune Jana
Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Stanford Cardiovascular Institute, School of Medicine, Stanford University, Stanford, California, United States.
Am J Physiol Lung Cell Mol Physiol. 2023 Apr 1;324(4):L550-L556. doi: 10.1152/ajplung.00379.2022. Epub 2023 Mar 7.
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, -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 -deficient mice compared with WT controls. Adverse RV remodeling was enhanced in -deficient PAB animals, evidenced by increased RV expression levels of connective tissue growth factor (), transforming growth factor-β (), and atrial natriuretic peptide (). In summary, deficiency exacerbates maladaptive RV remodeling and causes signs of RV dysfunction.
应激状态下的右心室（RV）特别容易产生和积累活性氧，导致细胞外基质沉积和利钠肽分泌。具有抗氧化能力的特定酶，如谷胱甘肽过氧化物酶3（GPx3），在右心室发病机制中的作用目前尚不清楚。在此，我们使用肺动脉环扎（PAB）小鼠模型来研究GPx3在孤立性右心室病理中的作用。与接受PAB手术的野生型（WT）小鼠相比，缺乏GPx3的PAB小鼠表现出更高的右心室收缩压和更高的左心室偏心指数。与WT对照组相比，缺乏GPx3的小鼠中，PAB诱导的富尔顿指数、右心室游离壁厚度和右心室面积分数变化更为明显。在缺乏GPx3的PAB动物中，不良的右心室重塑增强，这通过右心室中结缔组织生长因子（CTGF）、转化生长因子-β（TGF-β）和心钠素（ANP）表达水平的增加得到证明。总之，GPx3缺乏会加剧适应性不良的右心室重塑，并导致右心室功能障碍的迹象。
