Divergent transcriptional responses to independent genetic causes of cardiac hypertrophy

Citation
Bj. Aronow et al., Divergent transcriptional responses to independent genetic causes of cardiac hypertrophy, PHYSIOL GEN, 6(1), 2001, pp. 19-28
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
PHYSIOLOGICAL GENOMICS
ISSN journal
1094-8341 → ACNP
Volume
6
Issue
1
Year of publication
2001
Pages
19 - 28
Database
ISI
SICI code
1094-8341(200106)6:1<19:DTRTIG>2.0.ZU;2-X
Abstract
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.