Therapeutic targeting of mitochondrial ROS ameliorates murine model of volume overload cardiomyopathy

Publication date: Available online 28 September 2019Source: Journal of Pharmacological SciencesAuthor(s): Kenichi Okamura, Yu Nakagama, Norihiko Takeda, Katsura Soma, Tatsuyuki Sato, Takayuki Isagawa, Yasutoshi Kido, Masaya Sakamoto, Ichiro Manabe, Yasutaka Hirata, Issei Komuro, Minoru OnoAbstractConcomitant heart failure is associated with poor clinical outcome in dialysis patients. The arteriovenous shunt, created as vascular access for hemodialysis, increases ventricular volume-overload, predisposing patients to developing cardiac dysfunction. The integral function of mitochondrial respiration is critically important for the heart to cope with hemodynamic overload. The involvement, however, of mitochondrial activity or reactive oxygen species (ROS) in the pathogenesis of ventricular-overload-induced heart failure has not been fully elucidated.We herein report that disorganization of mitochondrial respiration increases mitochondrial ROS production in the volume-overloaded heart, leading to ventricular dysfunction. We adopted the murine arteriovenous fistula (AVF) model, which replicates the cardinal features of volume-overload-induced ventricular dysfunction. Enzymatic assays of cardiac mitochondria revealed that the activities of citrate synthase and NADH-quinone reductase (complex Ⅰ) were preserved in the AVF heart. In contrast, the activity of NADH oxidase supercomplex was significantly compromised, resulting in elevated ROS production. Importantly, the antioxidant N-a...
Source: Journal of Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research