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Elucidating the molecular mechanism of cardiac remodeling using a comparative genomic approach

¹ Cardiovascular Research, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115
² Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037

It is proposed that analysis of global gene expression would provide an understanding of the molecular mechanisms of cardiac remodeling. However, previous studies have only provided "snapshots" of differential gene expression. Furthermore, the differences in gene expression between regions of the heart that can result in sampling variability have not been characterized. In this study, we employed the Affymetrix GeneChip technology to evaluate the patterns of expression in two different in vivo models of cardiac remodeling and in two different regions (left ventricle free wall and intraventricular septum) of the heart. Mice underwent transverse aortic constriction (TAC), myocardial infarction (MI), or sham operation, and RNA from the left ventricle free wall and the septum was isolated 1 wk later. Histological analysis showed profound myocyte hypertrophy and fibrosis in both the septum and the left ventricle free wall of the TAC model, whereas, in the MI model, only the left ventricle exhibited hypertrophy. These differences were also reflected in the expression analysis. In conclusion, our analysis shows that regional differences in gene expression exist in the heart. Moreover, common pathways that are coregulated in both models exist, and these might be central to the hypertrophic phenotype regardless of the initial hypertrophic stimuli.

left ventricle; septum; myocardial infarction; aorta constriction; cardiac hypertrophy; gene expression

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