Abstract 11928: Cardiospecific Overexpression of Carnosine Synthase Attenuates Myocardial Ischemia Reperfusion Injury

Even though myocardial ischemia/reperfusion (I/R) remains the leading cause of death, the underlying mechanisms remain incompletely understood. Increased formation of reactive carbonyl has been shown to be a common biochemical feature of I/R injury. These carbonyls are generated from the oxidation of proteins and membrane lipids. Reactive carbonyls such as methylglyoxal are generated from increased glycolytic activity during ischemia. Previous work in our lab has shown that the endogenous dipeptide carnosine (β-alanine-histidine) quenches both protein and lipid derived carbonyls. It can also buffer changes in intracellular pH and chelate metals that catalyze ROS production. In the heart, carnosine is synthesized by the ATP grasp enzyme (ATPGD1). Hence, we examined whether overexpression of ATPGD1 could increase carnosine synthesis in the heart and attenuate I/R injury. To overexpress ATPGD1, we generated mice in which the expression of the transgene was driven by cardiospecific α-MHC promoter. Two differe...