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

Background-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 tiss ue samples to study developmental transitions and the response to myocardia l infarction (MI). Methods and Results-Microarrays with rat cDNAs for 86 known genes and 989 a nonymous cDNAs obtained by molecular subtraction (representational differen ce analysis) of mRNA from sham-operated and 6-week post-MI samples were use d in 2-color hybridization experiments. Twelve known genes previously assoc iated with myocardial development were identified together with 10 uncharac terized 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 hyb ridization revealed mRNA localization characteristic of wound healing and v ascular and cardiomyocyte reactivity. Conclusions-Tissue analysis of gene expression with cDNA microarrays provid es a measure of transcriptional or posttranscriptional regulation and cellu lar 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.