Transcript profiling of global PKM2 knockout mouse hearts to evaluate the cardiac role of PKM2 after myocardial infarction

During myocardial infarction (MI), energy production decreases as hypoxia inhibits oxidative metabolism. Our lab has identified an ischemia-regulated alternative splicing event of the glycolytic enzyme pyruvate kinase (muscle, PKM), reducing PKM1 expression and increasing PKM2 expression. We hypothesized the upregulation of PKM2 aids in energy production to maintain heart function after MI. We utilized high-throughput sequencing to evaluate altered gene expression and identify pathways that may be regulated by PKM2. Overall design: To investigate the role of PKM2 during MI, we generated global PKM2 knockout mice. We then performed gene expression profiling analysis using RNA-seq of knockout and control left ventricle tissue at baseline, or 3 days after sham surgery or ligation of the left anterior descending artery (LAD). At the time of harvest, tissue was flash frozen, and then pulverized before RNA extraction. Sham mice were used as controls for MI samples. Two biological replicates were used for baseline samples and three biological replicates for sham and MI samples per genotype.