Figure 4. Cardiac mechanotransduction signalling.

Cardiac myocytes respond to altered haemodynamics by activating multiple intracellular signalling pathways that are implicated in the maintenance and regulation of cardiac myocyte fucntion. Mechanical loading can be sensed by cardiomyocytes through a diverse group of membrane anchored mechanosensors including stretch activated ion channels, cell membrane - spanning G-protein coupled receptors, growth factor receptors, and integrins. This mechanical sensation is then converted to biochemical signals by triggering the multi-step activation of downstream partners in an array of signalling cascades in the cytoplasm. The highlights of such cascades include the three modules of the MAPK family underscored by the activation of Ras, the JAK-STAT pathway, Rac activation, calcium and NO signalling. The convergence of these pathways results in the activation of select transcription factors including NF-AT and NF-kB which then translocate to the nucleus and modulate the expression of a panel of mechanosenstive genes including egr-1 and iex-1. Ultimately, the net sum of gene expression reprogramming in cardiomyocytes dictates the functional response of the cell to mechanical stress.