Application of cDNA microarrays in determining molecular phenotype in cardiac growth, development, and response to injury.

Normal myocardial development and the tissue response to cardiac stress are accompanied by marked changes in gene expression; however, the extent of these changes and their significance remain to be fully explored. We used cDNA microarrays for gene expression profiling in rat cardiac tissue samples to study developmental transitions and the response to myocardial infarction (MI). Microarrays with rat cDNAs for 86 known genes and 989 anonymous cDNAs obtained by molecular subtraction (representational difference analysis) of mRNA from sham-operated and 6-week post-MI samples were used in 2-color hybridization experiments. Twelve known genes previously associated with myocardial development were identified together with 10 uncharacterized expressed sequence tags and 36 genes not previously associated with cardiac development. After MI, genes associated with myocardial stress and wound healing exhibited differences in magnitude and expression kinetics, and 14 genes not previously associated with MI were identified. In situ hybridization revealed mRNA localization characteristic of wound healing and vascular and cardiomyocyte reactivity. Tissue analysis of gene expression with cDNA microarrays provides a measure of transcriptional or posttranscriptional regulation and cellular recruitment. Our results demonstrate the complexity of gene regulation in the developing myocardium and show that cDNA microarrays can be used to monitor the evolution of the cardiac stress-inducible phenotype.