INTERMEDIATE FILAMENT-MEDIATED STRETCH-INDUCED CHANGES IN CHROMATIN -A HYPOTHESIS FOR GROWTH INITIATION IN CARDIAC MYOCYTES

Excessive stretching of the myocardium leads to hypertrophy, but how t he stretch message is communicated to hypertrophy-initiating genes is unknown. Candidates hypothesized as couplers of physical stretch to gr owth initiation include neural and hormonal factors, stretch-activated and stretch-inactivated ion channels, microtubules, microfilaments, a nd contractile activity. Upon investigation, however, all were ruled o ut. 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-labe ling technique, we found that when cardiac myocytes are stretched ther e are changes in the spatial arrangement of both the desmin-lamin inte rmediate filament network and the nuclear-envelope-associated chromati n. We hypothesize that (a) by physically linking the sarcomere to chro matin, the desmin-lamin intermediate filament network couples sarcomer e length to chromatin distribution, and (b) stretch-induced changes in chromatin (mediated by the intermediate filament network) activate hy pertrophy-associated genes. Further investigation is needed to test th is hypothesis. (C) 1996 Academic Press Limited