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 componen t of the differential growth adaptation of the right and left ventricl e during development, the formation of DNA strand breaks in myocyte nu clei was identified and quantitated in hearts of rats at the end of ge station and at 1, 5, 11, and 21 days after birth. Incorporation of Brd U in left and right ventricular myocytes was also evaluated. Moreover, the expression of bcl-2 in myocytes was determined. Programmed myocyt e 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 exhi bited DNA degradation at 1 day in the right ventricle, interventricula r 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/10,00 0 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 v entricle at 1, 5, and 11 days was statistically significant. In contra st, BrdU incorporation in myocytes decreased in a comparable manner in the left and right ventricles with maturation. Importantly, bcl-2 mRN A levels were high in fetal myocytes, decreased markedly at 1 and 5 da ys, and progressively increased at II and 21 days. The expression of b cl-2 was lower in right than in left ventricular myocytes. In conclusi on, programmed myocyte cell death is inversely related to bcl-2 expres sion and affects the right ventricle more than the left ventricle duri ng postnatal development. This phenomenon may be crucial in the modula tion of the number of myocytes in the two ventricles during the transi tion from the fetal to the adult circulatory system. (C) 1995 Academic Press, Inc.