INSULIN-LIKE GROWTH-FACTOR-I STIMULATES MYOFIBRIL DEVELOPMENT AND DECREASES SMOOTH-MUSCLE ALPHA-ACTIN OF ADULT CARDIOMYOCYTES

Adult rat cardiomyocytes in long-term culture express type 1 insulin-l ike growth factor (IGF) receptors. In contrast to insulin receptors, t ype 1 IGF receptors are up-regulated during culturing. IGF-I added to the cells at plating increased granular density and pseudopodia number per cell after 7 days. After 16 days, IGF-I-treated cells showed, as compared with controls, a dramatic increase of the number of newly bui lt sarcomeres and were packed with myofibrils. At the same time, IGF-I suppressed the accumulation of smooth muscle alpha-actin (sm-alpha-ac tin) in a dose-dependent manner. Under the conditions of this in vitro system, growth hormone had no effect on cell morphology or sm-alpha-a ctin. sm-alpha-Actin, a nonsarcomeric isoform of actin expressed in ea rly fetal cardiac development, reappears both during long-term culture of adult rat cardiomyocytes and during heart hypertrophy. This study shows that type 1 IGF receptors are up-regulated in adult rat cardiomy ocytes in long-term culture and that IGF-I enhances myofibril developm ent and concomitantly down-regulates sm-alpha-actin. This protein form s stress-fiber like structures and may temporarily serve as a scaffold for the formation of new sarcomeres until myofibrils have developed t hroughout the cell and the scaffold is no longer needed. Our findings thus allow us to propose another hypothesis for the mechanism leading to overload heart hypertrophy.