[Molecular adaptation of the heart to hypertension].
Because myocardial hypertrophy is an independent risk factor for sudden death and cardiac failure, it is important to understand its molecular mechanisms to be able to devise new treatment strategies in the future. Stretch is the putative primary stimulus triggering hypertrophy. Further signal transduction steps such as auto- and paracrine secretion of growth factors or transmission via the cytoskeleton are beginning to be unravelled. Subsequent to hypertrophic stimuli some important proteins undergo an isoform switch; questitatively, however, the most important step is an increase in translational capacity for each mRNA. Myocardial specific gene expression is achieved by coordinate interaction of several transcription factors, some of which may be involved in nuclear transmission of hypertrophic signals. One of the genes capable of transmitting hypertrophic signals is the "early growth response gene-1 (Egr-1)". We have also shown that nuclear estrogen receptors act as transcription factors in the myocardium and may therefore be involved in the sex-specific modulation of cardiac hypertrophy. At present, 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 are composed of a series of proteinkinases which may be amenable to drugs. In the future, gene transfer may become an option for treatment.
Neyses
L
L
Medizinische Universitätsklinik Würzburg.
Pelzer
T
T
D000818:Animals; D006332:Cardiomegaly / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D051766:Early Growth Response Protein 1; D004967:Estrogens / Q000502:physiology; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000473:pathology; D017874:Immediate-Early Proteins; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D004967:Estrogens; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D014157:Transcription Factors