Identification of differentially expressed genes in cardiac hypertrophy byanalysis of expressed sequence tags

Cardiac hypertrophy is an adaptive response to chronic hemodynamic overload . We employed a whole-genome approach using expressed sequence tags (ESTs) to characterize gene transcription and identify new genes overexpressed in cardiac hypertrophy. Analysis of general transcription patterns revealed a proportional increase in transcripts related to cell/organism defense and a decrease in transcripts related to cell structure and motility in hypertro phic hearts compared to normal hearts. Detailed comparison of individual ge ne expression identified 64 genes potentially overexpressed in hypertrophy, of 232 candidate genes derived from a set of 77,692 cardiac ESTs, includin g 47,856 ESTs generated in our laboratory. Of these, 29 were good candidate s (P < 0.0002) and 35 were weaker candidates (P < 0.005). RT-PCR of a numbe r of these candidate genes demonstrated correspondence of EST-based predict ions of gene expression with irt vitro levels. Consistent with an organ und er various stresses, up to one-half of the good candidates predicted to exh ibit differential expression were genes potentially involved in stress resp onse. Analyses of general transcription patterns and of single-gene express ion levels were also suggestive of increased protein synthesis in the hyper trophic myocardium, Overall, these results depict a scenario compatible wit h current understanding of cardiac hypertrophy. However, the identification of several genes not previously known to exhibit increased expression in c ardiac hypertrophy (e.g., prostaglandin D synthases; CD59 antigen) also sug gests a number of new avenues for further investigation. These data demonst rate the utility of genome-based resources for investigating questions of c ardiovascular biology and medicine. (C) 2000 Academic Press.