Cardiomyocyte proliferation contributes to heart growth in young humans

TLDR

The human heart is thought to grow by enlargement rather than cardiomyocyte proliferation after birth, yet recent animal studies and evidence of adult cardiomyocyte turnover suggest proliferation may contribute to developmental heart growth between birth and adolescence. The study aimed to test whether cardiomyocyte proliferation contributes to left ventricular growth in humans aged 0–59 years. The authors examined left ventricular cellular growth mechanisms in 36 healthy human hearts spanning ages 0–59 years. Cardiomyocyte mitosis peaks in infants and declines by age 20, with cytokinesis absent after 20 years; between birth and 20 years the left ventricular cardiomyocyte number increased 3.4‑fold, confirming that proliferation drives developmental heart growth and implying potential regenerative capacity in children and adolescents and possible therapeutic targets for pediatric myocardial disease.

Abstract

The human heart is believed to grow by enlargement but not proliferation of cardiomyocytes (heart muscle cells) during postnatal development. However, recent studies have shown that cardiomyocyte proliferation is a mechanism of cardiac growth and regeneration in animals. Combined with evidence for cardiomyocyte turnover in adult humans, this suggests that cardiomyocyte proliferation may play an unrecognized role during the period of developmental heart growth between birth and adolescence. We tested this hypothesis by examining the cellular growth mechanisms of the left ventricle on a set of healthy hearts from humans aged 0–59 y ( n = 36). The percentages of cardiomyocytes in mitosis and cytokinesis were highest in infants, decreasing to low levels by 20 y. Although cardiomyocyte mitosis was detectable throughout life, cardiomyocyte cytokinesis was not evident after 20 y. Between the first year and 20 y of life, the number of cardiomyocytes in the left ventricle increased 3.4-fold, which was consistent with our predictions based on measured cardiomyocyte cell cycle activity. Our findings show that cardiomyocyte proliferation contributes to developmental heart growth in young humans. This suggests that children and adolescents may be able to regenerate myocardium, that abnormal cardiomyocyte proliferation may be involved in myocardial diseases that affect this population, and that these diseases might be treatable through stimulation of cardiomyocyte proliferation.