PI3K(p110 alpha) Protects Against Myocardial Infarction-Induced Heart Failure Identification of PI3K-Regulated miRNA and mRNA

Objective— Myocardial infarction (MI) is a serious complication of atherosclerosis associated with increasing mortality attributable to heart failure. Activation of phosphoinositide 3-kinase [PI3K(p110α)] is considered a new strategy for the treatment of heart failure. However, whether PI3K(p110α) provides protection in a setting of MI is unknown, and PI3K(p110α) is difficult to target because it has multiple actions in numerous cell types. The goal of this study was to assess whether PI3K(p110α) is beneficial in a setting of MI and, if so, to identify cardiac-selective microRNA and mRNA that mediate the protective properties of PI3K(p110α). Methods and Results— Cardiomyocyte-specific transgenic mice with increased or decreased PI3K(p110α) activity (caPI3K-Tg and dnPI3K-Tg, respectively) were subjected to MI for 8 weeks. The caPI3K-Tg subjected to MI had better cardiac function than nontransgenic mice, whereas dnPI3K-Tg had worse function. Using microarray analysis, we identified PI3K-regulated miRNA and ...