AGING DOES NOT AFFECT THE ACTIVATION OF THE MYOCYTE INSULIN-LIKE GROWTH-FACTOR-I AUTOCRINE SYSTEM AFTER INFARCTION AND VENTRICULAR FAILURE IN FISCHER-344 RATS

To determine whether the attenuation in the growth capacity of myocyte s in the overloaded aging heart is associated with an impairment in th e activation of insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) in the stressed cells, large myocardial infarcts were produce d in Fischer 344 rats at 4 and 16 months of age, and the animals were killed 6 hours, 3 days, and 7 days later. After the documentation of c ardiac failure, the unaffected myocytes were enzymatically dissociated , and the expression of IGF-1 and IGF-1R was measured at these three t ime points after surgery. The level of expression of IGF-1R mRNA incre ased at 3 days and remained elevated at 7 days in both age groups. In addition, an increase in IGF-1R protein in these cells was found, with no apparent difference with age. This phenomenon was coupled with an upregulation of IGF-1 mRNA of comparable magnitude in the younger and older animals. In contrast, the increases in the dimensional propertie s of myocytes were delayed and of smaller magnitude in the older infar cted rats. Moreover, the expression of atrial natriuretic factor, used as a molecular marker of myocyte cellular hypertrophy, was greater at 3 days in 4-month-old rats and at 7 days in 16-month-old rats. Thus. aging may affect the hypertrophic response of myocytes after infarctio n but has no impact on the ability of the cells to enhance the express ion of IGF-1 and IGF-1R, which may sustain only in part the growth res erve mechanisms of the pathological heart.