To define molecular mechanisms of cardiac hypertrophy, genes whose expressi
on was perturbed by any of four different transgenic mouse hypertrophy mode
ls [protein kinase C-epsilon activation peptide (Psi epsilon RACK), calsequ
estrin (CSQ), calcineurin (CN), and G alphaq] were compared by DNA microarr
ay analyses using the similar to8,800 genes present on the Incyte mouse GEM
1. The total numbers of regulated genes (tens to hundreds) correlated with
phenotypic severity of the model (G alphaq > CN > CSQ > Psi epsilon RACK),
but demonstrated that no single gene was consistently upregulated. Of the t
hree models exhibiting pathological hypertrophy, only atrial natriuretic pe
ptide was consistently upregulated, suggesting that transcriptional alterat
ions are highly specific to individual genetic causes of hypertrophy. Howev
er, hierarchical-tree and K-means clustering analyses revealed that subsets
of the upregulated genes did exhibit coordinate regulatory patterns that w
ere unique or overlapping across the different hypertrophy models. One stri
king set consisted of apoptotic genes uniquely regulated in the apoptosis-p
rone G alphaq model. Thus, rather than identifying a single common hypertro
phic cardiomyopathy gene program, these data suggest that extensive groups
of genes may be useful for the prediction of specific underlying genetic de
terminants and condition-specific therapeutic approaches.