DNA polymerases during postnatal myocardial development.

Abstract

THE rate of mitotic division of cardiac muscle cells declines rapidly during late embryonic and early postnatal development1–5 pari passu with a progressive restriction in proliferative capacity2,3. Adaptation of adult myocardium to increased functional demand is thus limited to hypertrophy, that is, an increase in size of individual cells without a change in their number. In contrast, non-muscle cardiac cells (interstitial and endothelial cells) retain their capacity to proliferate in response to appropriate stimuli6. The mechanisms controlling proliferation in the developing myocardium are not known. Several investigators have noted, however, a close temporal correlation between the age-dependent decline in mitotic activity and reduced levels of enzymes involved in DNA synthesis7–9. The possibility has been raised5 that this enzyme loss is, in fact, responsible for the inability of adult myocardial cells to undergo mitosis. Here we describe differential changes in the activities of DNA polymerases from cardiac muscle and non-muscle cells during the postnatal development of the rat heart and suggest that changes in these enzymes are not sufficient explanation for the restriction in proliferative capacity.