Module 12: Figure hypertrophy signalling mechanisms

Remodelling the cardiac signalsome during compensatory hypertrophy.

A number of signalling pathways have been implicated in the activation of the transcription factors responsible for switching on the foetal genes that remodel the signalsome. One important action of Ca2+ is to stimulate the calcineurin (CaN)/nuclear factor of activated T cells (NFAT) pathway. Ca2+ released from inositol 1,4,5-trisphosphate (InsP3) receptors (I) in the vicinity of the nucleus has been implicated in controlling the histone deacetylase (HDAC) shuttle. The mitogen-activated protein kinase (MAPK) pathway may contribute to hypertrophy by activating the transcription factor cyclic AMP response element-binding protein (CREB). The PtdIns 3-kinase signalling pathway has several functions: it can inhibit apoptosis, it facilitates the NFAT shuttle by inhibiting glycogen synthase kinase-3 (GSK-3), and it stimulates protein synthesis, which contributes to the increase in size of the heart. An animated version of this figure is available.