PROGRAMMED CELL-DEATH AND EXPRESSION OF THE PROTOONCOGENE BCL-2 IN MYOCYTES DURING POSTNATAL MATURATION OF THE HEART

To determine whether programmed myocyte cell death is a major component of the differential growth adaptation of the right and left ventricle during development, the formation of DNA strand breaks in myocyte nuclei was identified and quantitated in hearts of rats at the end of gestation and at 1, 5, 11, and 21 days after birth. Incorporation of BrdU in left and right ventricular myocytes was also evaluated. Moreover, the expression of bcl-2 in myocytes was determined. Programmed myocyte cell death was absent in the fetal heart but affected the myocardium postnatally. This phenomenon was no longer detectable at 21 days. DNA strand breaks in nonmyocyte nuclei were present at all time intervals. Quantitatively, 10.4, 6.1, and 2.5 myocyte nuclei/10,000 nuclei exhibited DNA degradation at 1 day in the right ventricle, interventricular septum, and left ventricle, respectively. Corresponding values at 5 days were 3.7, 3.5, and 2.0 myocyte nuclei/10,000 nuclei. At 11 days, programmed cell death involved 1.2, 1.5, and 0.53 myocyte nuclei/10,000 nuclei in these three regions of the heart. The 4.2-fold, 1.9-fold, and 2.3-fold greater magnitude of programmed cell death in the right ventricle at 1, 5, and 11 days was statistically significant. In contrast, BrdU incorporation in myocytes decreased in a comparable manner in the left and right ventricles with maturation. Importantly, bcl-2 mRNA levels were high in fetal myocytes, decreased markedly at 1 and 5 days, and progressively increased at II and 21 days. The expression of bcl-2 was lower in right than in left ventricular myocytes. In conclusion, programmed myocyte cell death is inversely related to bcl-2 expression and affects the right ventricle more than the left ventricle during postnatal development. This phenomenon may be crucial in the modulation of the number of myocytes in the two ventricles during the transition from the fetal to the adult circulatory system. (C) 1995 Academic Press, Inc.