INFLUENCE OF FIBROBLAST GROWTH-FACTOR (BFGF) AND INSULIN-LIKE GROWTH-FACTOR (IGF-I) ON CYTOSKELETAL AND CONTRACTILE STRUCTURES AND ON ATRIAL-NATRIURETIC-FACTOR (ANF) EXPRESSION IN ADULT-RAT VENTRICULAR CARDIOMYOCYTES IN CULTURE

The effects of basic fibroblast growth factor (bFGF) and of insulin-li ke growth factor-I (IGF-I) on structural (actin cytoskeleton and myofi brillar apparatus remodeling and on the expression of atrial natriuret ic factor (ANF) in adult rat ventricular cardiomyocytes have been foll owed during the hypertrophy reaction up to 3 weeks in culture. Cells a ttach to the substratum, spread into polygonal shapes with pseudopodia and resume contractile function after 1 week. A well structured actin cytoskeleton with stress fiber-like structures ails the cell bodies a nd the extensions. In controls and with IGF-I cells grow to the double volume while bFGF induces a four-fold increase. The myofibrillar appa ratus follows the actin stress fiber-like structures in growing out in to the cell periphery. Immunoreactive ANF granules develop and are con centrated around the nuclear region. The fetally occurring alpha-smoot h muscle actin (alpha-sm-actin) is re-expressed in stress fiber-like s tructures. IGF-I down-regulates alpha-sm-actin and ANF and promotes my ofibrillar growth whereas bFGF has the opposite effect by up-regulatin g alpha-sm-actin (on average five to six times more than in controls a s analysed by immunoblotting) and ANF. In addition, bFGF restricts myo fibrillar growth with a sharp boundary in the perinuclear region. The most dense packing of alpha-sm-actin in the cytoskeleton is found just outside the area containing the myofibrils; so alpha-sm-actin seems t o restrict myofibrillar assembly and growth. These cells are neverthel ess beating like the controls. The relative increase of cytoskeletal s tructures with the concomitant lack of growth of myofibrils, is mostly due to an increase in alpha-sarcomeric actin ice-cardiac and alpha-sk eletal muscle actin) and in alpha-sm-actin. (C) 1996 Academic Press Li mited