THE BIOLOGICAL CASCADE LEADING TO CARDIAC-HYPERTROPHY

Cardiac hypertrophy, one of the major risk factors in hypertension is associated with a high incidence of congestive heart failure and sudde n death. Despite efforts over the last 20 years, the underlying molecu lar mechanisms of cardiac hypertrophy are still poorly understood thus making it difficult to develop new therapeutic strategies. A growing body of evidence suggests that cardiac hypertrophy results from mechan ical stress that triggers paracrine and autocrine signal transduction pathways. Furthermore, whereas hypertrophy leads to isoform switches i n some contractile proteins, increased protein synthesis is largely ba sed on increased translational capacity. Cardiac growth under physiolo gical as well as pathological conditions is regulated by several recen tly identified transcription factors. Among the factors that are capab le of transmitting hypertrophic stimuli to the nucleus is the early gr owth response gene-1 (Egr-1). Whereas eas female gender is already an established cardioprotective factor in clinical trials, some very rece nt data indicate that oestrogens and the nuclear oestrogen receptor my directly modulate gene expression in the development of cardiac hyper trophy. Future pharmacological interventions could be directed towards modifying the nuclear signal transduction cascade involving multiple protein kinases and phosphatases.