Divergent transcriptional responses to independent genetic causes of cardiac hypertrophy

Bruce J. Aronow, Tsuyoshi Toyokawa, Amy Canning, Kobra Haghighi, Ulrike Delling, Evangelia Kranias, Jeffery D. Molkentin, Gerald W. Dorn

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


To define molecular mechanisms of cardiac hypertrophy, genes whose expression was perturbed by any of four different transgenic mouse hypertrophy models [protein kinase C-ε activation peptide (ΨεRACK), calsequestrin (CSQ), calcineurin (CN), and Gαq] were compared by DNA microarray analyses using the ∼8,800 genes present on the Incyte mouse GEM1. The total numbers of regulated genes (tens to hundreds) correlated with phenotypic severity of the model (Gαq > CN > CSQ > ΨεRACK), but demonstrated that no single gene was consistently upregulated. Of the three models exhibiting pathological hypertrophy, only atrial natriuretic peptide was consistently upregulated, suggesting that transcriptional alterations are highly specific to individual genetic causes of hypertrophy. However, hierarchical-tree and K-means clustering analyses revealed that subsets of the upregulated genes did exhibit coordinate regulatory patterns that were unique or overlapping across the different hypertrophy models. One striking set consisted of apoptotic genes uniquely regulated in the apoptosis-prone Gαq model. Thus, rather than identifying a single common hypertrophic cardiomyopathy gene program, these data suggest that extensive groups of genes may be useful for the prediction of specific underlying genetic determinants and condition-specific therapeutic approaches.

Original languageEnglish
Pages (from-to)19-28
Number of pages10
JournalPhysiological genomics
Issue number1
StatePublished - Sep 2001


  • Cardiac hypertrophy
  • DNA microarray
  • Gene expression
  • Transgenic mouse


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