Expression profiling reveals distinct sets of genes altered during induction and regression of cardiac hypertrophy

Although cardiac hypertrophy has been the subject of intensive investigatio n, regression of hypertrophy has been significantly less studied, precludin g large-scale analysis of the relationship between these processes. In the present study, using pharmacological models of cardiac hypertrophy in mice, expression profiling was performed with fragments of more than 4,000 genes to characterize and contrast expression changes during induction and regre ssion of hypertrophy. Administration of angiotensin II and isoproterenol by osmotic minipump produced increases in heart weight (15 and 45%, respectiv ely) that returned to preinduction size after drug withdrawal. From multipl e expression analyses of left ventricular RNA isolated at daily time-points during cardiac hypertrophy and regression, we identified sets of genes who se expression was altered at specific stages of this process. While confirm ing the participation of 25 genes or pathways previously shown to be altere d by hypertrophy, a larger set of 30 genes was identified whose expression had not previously been associated with cardiac: hypertrophy or regression. Of the 55 genes that showed reproducible changes during the time course of induction and regression. 32 genes were altered only during induction, and 8 were altered only during regression. This study identified both known an d novel genes whose expression is affected at different stages of cardiac h ypertrophy and regression and demonstrates that cardiac remodeling during r egression utilizes a set of genes that are distinct from those used during induction of hypertrophy.