Signal transduction and transcriptional adaptation in embryonic heart development and during myocardial hypertrophy.

In comparing the pathological state of cardiac hypertrophy with early embryonic growth and development of the primitive heart, important and informative aspects of mechanisms that underlie activation of the gene expression pattern become apparent. Interestingly, in both cases the muscle phenotypes share the expression of a 'fetal' gene expression program, raising the question whether the same genetic mechanism is being called upon by signals associated with the onsets of cardiogenesis and myocardial hypertrophy. A cell specific transcription factor, CLP-1, was recently identified in our laboratory that is likely to play a crucial role, in conjunction with other known regulatory factors, in early cardiac events leading to cardiogenic cell specification and differentiation. We have also identified a novel mechanism that involves activation of the Jak/Stat signaling pathway that is linked to the autocrine angiotensin-II loop associated with the hypertrophic response in cardiomyocytes. Since early cardiac cell development and the hypertrophic state involve the expression of the same battery of genes, one may speculate that common transcription factors may account for assembling a competent apparatus responsible for transcribing the genes. Our present studies are designed to investigate the potential role of these factors in control of both processes.