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 sudden death. Despite efforts over the last 20 years, the underlying molecular 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 mechanical stress that triggers paracrine and autocrine signal transduction pathways. Furthermore, whereas hypertrophy leads to isoform switches in some contractile proteins, increased protein synthesis is largely based on increased translational capacity. Cardiac growth under physiological as well as pathological conditions is regulated by several recently identified transcription factors. Among the factors that are capable of transmitting hypertrophic stimuli to the nucleus is the early growth response gene-1 (Egr-1). Whereas female gender is already an established cardioprotective factor in clinical trials, some very recent data indicate that oestrogens and the nuclear oestrogen receptor may directly modulate gene expression in the development of cardiac hypertrophy. Future pharmacological interventions could be directed towards modifying the nuclear signal transduction cascade involving multiple protein kinases and phosphatases.
Neyses
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L
Department of Cardiology, University of Würzburg, Germany.
Pelzer
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T
D006332:Cardiomegaly / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D051766:Early Growth Response Protein 1; D004967:Estrogens / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D017874:Immediate-Early Proteins; D008297:Male; D009206:Myocardium / Q000473:pathology; D011960:Receptors, Estrogen / Q000502:physiology; 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; D011960:Receptors, Estrogen; D014157:Transcription Factors