Intermediate filament-mediated stretch-induced changes in chromatin: a hypothesis for growth initiation in cardiac...

Excessive stretching of the myocardium leads to hypertrophy, but how the stretch message is communicated to hypertrophy-initiating genes is unknown. Candidates hypothesized as couplers of physical stretch to growth initiation include neural and hormonal factors, stretch-activated and stretch-inactivated ion channels, microtubules, microfilaments, and contractile activity. Upon investigation, however, all were ruled out. We provide evidence here that it is the intermediate filaments in the mechanically stressed myocyte that transmit the stretch message to the chromatin. Using rat myocytes and an immunogold desmin-lamin-labeling technique, we found that when cardiac myocytes are stretched there are changes in the spatial arrangement of both the desmin-lamin intermediate filament network and the nuclear-envelope-associated chromatin. We hypothesize that (a) by physically linking the sarcomere to chromatin, the desmin-lamin intermediate filament network couples sarcomere length to chromatin distribution, and (b) stretch-induced changes in chromatin (mediated by the intermediate filament network) activate hypertrophy-associated genes. Further investigation is needed to test this hypothesis.