MOLECULAR ADAPTATION OF THE HEART IN HYPE RTROPHY

Because myocardial hypertrophy is an independent risk factor for sudde n death and cardiac failure, it is important to understand its molecul ar mechanisms to be able to devise new treatment strategies in the fut ure. Stretch is the putative primary stimulus triggering hypertrophy. Further signal transduction steps such as auto- and paracrine secretio n of growth factors or transmission via the cytoskeleton are beginning to be unravelled. Subsequent to hypertrophic stimuli some important p roteins undergo an isoform switch; questitatively, however, the most i mportant step is an increase in translational capacity for each mRNA. Myocardial specific gene expression is achieved by coordinate interact ion of several transcription factors, some of which may be involved in nuclear transmission of hypertrophic signals. One of the genes capabl e of transmitting hypertrophic signals is the ''early growth response gene-1 (Egr-1)''. We have also shown that nuclear estrogen receptors a ct as transcription factors in the myocardium and may therefore be inv olved in the sex-specific modulation of cardiac hypertrophy. At presen t, pharmacological interventions aiming at reduction of hypertrophy by interfering with the signal transduction pathway from the membrane to the nucleus are actively being sought. These transduction pathways ar e composed of a series of proteinkinases which may be amenable to drug s. In the future, gene transfer may become an option for treatment.