Genetic Expression Profiles During Physiologic and Pathologic Cardiac Hypertrophy and Heart Failure in Rats

Cardiac hypertrophy is a complex and non-homogenous response to various stimuli. In this study, we used high-density oligonucleotide microarray to examine gene expression profiles during physiologic hypertrophy, pathologic hypertrophy, and heart failure in Dahl salt-sensitive rats. There were changes in 404/3160 and 874/3160 genes between physiologic vs. pathologic hypertrophy and the transition from hypertrophy to heart failure, respectively. There were increases in stress response genes (e.g. heat shock proteins) and inflammation-related genes (e.g. PAP and Alox12) in pathologic processes but not in physiologic hypertrophy. Furthermore, atrial natriuretic factor (ANF) and brain natriuretic protein (BNP) showed distinctive changes that are very specific to different conditions. In addition, we used resampling-based gene score calculating method to define significantly altered gene clusters based on Gene Ontology (GO) classification. It revealed significant alterations in genes involved in the apoptosis pathway during pathologic hypertrophy suggesting that the apoptosis pathway may play a role during the transition to heart failure. In addition, there were significant changes in glucose/insulin signaling, protein biosynthesis and epidermal growth factor signaling during physiologic hypertrophy, but not during pathologic hypertrophy.