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.