PKCdelta causes sepsis-induced cardiomyopathy by inducing mitochondrial dysfunction.

PKCdelta causes sepsis-induced cardiomyopathy by inducing mitochondrial dysfunction. Am J Physiol Heart Circ Physiol. 2020 Mar 06;: Authors: Joseph LC, Reyes MV, Lakkadi KR, Gowen BH, Hasko G, Drosatos K, Morrow JP Abstract Sepsis-induced cardiomyopathy (SIC) is associated with increased patient mortality. At present, there are no specific therapies for SIC. Previous studies have reported increased ROS and mitochondrial dysfunction during SIC. However, a unifying mechanism remains to be defined. We hypothesized that PKCdelta is required for abnormal calcium handling and cardiac mitochondrial dysfunction during sepsis, and that genetic deletion of PKCdelta would be protective. Polymicrobial sepsis induced by cecal ligation and puncture (CLP) surgery decreased the ejection fraction of WT mice but not PKCdelta KO mice. Similarly, WT cardiomyocytes exposed to lipopolysaccharide (LPS) demonstrated decreases in contractility and calcium transient amplitude that were not observed in PKCdelta KO cardiomyocytes. LPS treatment decreased SR calcium stores in WT cardiomyocytes, which correlated with increased RYR2 oxidation in WT hearts but not PKCdelta KO hearts after sepsis. LPS exposure increased mitochondrial ROS and decreased mitochondrial inner membrane potential in WT cardiomyocytes. This corresponded to morphologic changes consistent with mitochondrial dysfunction such as decreased overall size, cristae disorganization. Increased cellula...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research