DOE Human Genome Program Contractor-Grantee Workshop VIII
February 27-March 2, 2000  Santa Fe, NM

106. Genome-Wide Expression Analysis Prove that Distinct Sets of Genes Participate in Cardiac Hypertrophy and the Regression of Hypertrophy

Carl Friddle, James Bristow, Teiichiro Koga, and Edward M. Rubin

Department of Genome Sciences, Lawrence Berkeley National Laboratory, Berkeley, CA 94720

EMRubin@lbl.gov

Cardiac hypertrophy is a significant risk factor for cardiac failure, affecting 15% of the adult population and 50% of those with hypertension. Single gene disorders account for a small fraction of these cases. Prior studies have identified a limited set of genes that play important roles in the onset progression and regression of cardiac hypertrophy. These studies have primarily focussed on genes known to function in the heart. In the present study, using pharmacological models of hypertrophy in mice, expression profiling was performed with fragments of more than 3,000 genes to characterize and contrast expression changes during induction and regression of hypertrophy. Administration of angiotensin II and isoproterenol by osmotic minipump produced increases in heart weight (15% and 40% respectively) that returned to pre-induction size following drug withdrawal. From multiple expression analyses of left ventricular RNA isolated at daily time-points during cardiac hypertrophy and regression, we identified sets of genes whose expression was altered at specific stages of this process. While confirming the participation of 25 genes and pathways known to be altered 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 and novel genes whose expression is affected at different stages of cardiac hypertrophy and regression and demonstrates that cardiac remodeling during regression utilizes a set of genes that are distinct from those used during induction of hypertrophy.