Proteomic analysis reveals different protein changes during endothelin-1- or leukemic inhibitory factor-induced hypertrophy of cardiomyocytes in vitro.

Proteomic analyses are being increasingly used to identify protein changes accompanying changes in cellular function. An advantage of this approach is that it is largely unbiased by prior assumptions on the importance of each protein in the process under investigation. Here we have evaluated the protein changes that accompany the enlargement, or hypertrophy, of cardiomyocytes in culture. We have taken the additional step of comparing the changes that accompany a concentric hypertrophic phenotype stimulated by endothelin-1 exposure and an eccentric hypertrophic phenotype stimulated by leukemic inhibitory factor exposure. Following separation of the protein extracts by two-dimensional gel electrophoresis and staining with colloidal Coomassie Brilliant Blue, we identified 15 protein spots representing 12 proteins that changed in response to endothelin-1. In comparison, 17 protein spots representing 17 proteins changed in response to leukemic inhibitory factor, and 35 protein spots representing 28 proteins did not change under these conditions. Importantly the well established marker of cardiac pathology, atrial natriuretic factor, was identified as a protein up-regulated by both endothelin-1 and leukemic inhibitory factor (2.4+/-0.8- and 2.2+/-0.3-fold, respectively). However, nine of the observed protein changes occurred for only endothelin-1, whereas 11 of the changes occurred only with leukemic inhibitory factor exposure. These two different stimuli are therefore able to elicit unique changes in the protein expression profile of cardiac myocytes. This is consistent with the differences in morphologies noted as well as the different signaling pathways utilized by these different stimuli.