Abstract P3171: Tubular Mitochondria Dysfunction Aki Induces Cardiac Malfunction In Cardiorenal Syndrome Type 3

Abstract

Cardiorenal syndrome type 3 (CRS 3) occurs when an acute kidney injury (AKI) leads to the development of cardiac dysfunction. It is associated with significant morbidity and mortality and is becoming increasingly prevalent. Mitochondrial dysfunction in renal tubular cells has been proposed as a critical regulator of AKI, but the exact mechanism of renal tubular mitochondrial dysfunction AKI-induced CRS 3 is still unclear. This study aims to characterize kidney and heart tissue injuries after AKI induced by maleic acid (MA). In an in vivo model, MA was used to induce AKI in C57BL/6 mice, and in an in vitro model, human proximal tubular epithelial cells (HK-2) were treated with MA. Our results showed that MA-induced AKI exacerbated renal tubular injury, increased the expression of renal injury molecule-1 (KIM-1), and caused apoptosis of renal tubular cells. At the cellular level, mitochondrial dysfunction was associated with increased mitochondrial reactive oxygen species (ROS), decreased coupling of mitochondrial respiration with decreased electron transport capacity, and reduced production of ATP. Transmission electron microscopy (TEM) examination revealed that mitochondrial cristae formation was defective in MA-induced AKI. Gene expression analysis revealed significantly lower ATPase6 levels and protein analysis confirmed that renal mitochondrial proteins of ATP subunits 5A1 and 5C1 were reduced considerably. The increase of NF-kB of the cardiac endothelial cell was observed with immunohistochemistry staining. Our study demonstrated that tubular mitochondrial dysfunction resulting from altered expression of ATP synthase is associated with AKI-induced type 3 cardiorenal syndrome, providing a potential novel target for developing new strategies for preventing and treating CRS3.