Adult rabbit cardiomyocytes undergo hibernation-like dedifferentiation when co-cultured with cardiac fibroblasts

Objectives: Little is known about the causal factors which induce the typic al structural changes accompanying cardiomyocyte dedifferentiation in vivo such as in chronic hibernating myocardium. For identifying important factor s involved in cardiomyocyte dedifferentiation, as seen in chronic hibernati on, an in vitro model mimicking those morphological changes, would be extre mely helpful. Methods: Adult rabbit cardiomyocytes were co-cultured with ca rdiac fibroblasts. The typical changes induced by this culturing paradigm w ere investigated using morphometry, electron microscopy and immunocytochemi cal analysis of several structural proteins, which were used as dedifferent iation markers, i.e., titin, desmin, cardiotin and alpha -smooth muscle act in. Results: Close apposition of fibroblasts with adult rabbit cardiomyocyt es induced hibernation-like dedifferentiation, similar to the typical chang es seen in chronic hibernation in vivo. Both changes in ultrastructure and in the protein expression pattern of dedifferentiation markers as seen in c hronic hibernating myocardium were seen in the co-cultured cardiomyocytes. Conclusion: Hibernation-like changes can be induced by co-culturing adult r abbit cardiomyocytes with fibroblasts. This cellular model can be a valuabl e tool in identifying and characterizing the pathways involved in the dedif ferentiation phenotype in vivo, and already suggests that many of the struc tural changes accompanying dedifferentiation are not per se dependent on a decreased oxygen availability. (C) 2001 Elsevier Science BY. All rights res erved.