APOPTOSIS IN PRESSURE OVERLOAD-INDUCED HEART HYPERTROPHY IN THE RAT

Pressure overload induces cardiac growth in the rat, which implies the hypertrophy of cardiac muscle cells and proliferation of nonmuscle ce lls, The cardiac cell loss observed in parallel has generally been att ributed to necrosis. Using an in situ assay, we demonstrated a phase o f apoptosis or programmed cell death during the first 7 d after pressu re overload with a peak at day 4 while cardiac growth continued for ov er 30 d, The increase in apoptosis was confirmed by quantification of 180-1500-bp DNA oligonucleosomes with agarose get electrophoresis and in situ labeling via 3'-terminal deoxynucleotidyl transferase assay. W hile some apoptosis was observed in the basal state in nonmuscle cells , pressure overload induced apoptosis mainly in cardiomyocytes. These data suggest that cardiac hypertrophy is initiated by a wave of apopto sis of cardiomyocytes. Thus, apoptosis may be involved in the pathogen esis of heart remodeling.