Abstract 15232: Cardiomyocyte Proliferation Contributes to Post-Natal Heart Growth in Humans
Post-natal growth of the human heart is considered to take place by enlargement of cardiomyocytes, the contractile cells of the heart muscle, without significant proliferation. In pre-natal heart growth, stem cell differentiation and cardiomyocyte proliferation are known to contribute to the expansion of the cardiomyocyte population. Recent studies suggest that cardiomyocyte proliferation could play a previously undocumented role post-natally as well. Understanding the role of cardiomyocyte proliferation in myocardial growth may provide a more comprehensive account of heart development as well as the basis for developing new strategies to treat heart failure. Analysis of postnatal heart growth was first evaluated at the organ level on a validated sample of 576 healthy people (age range 1 day-20 years) by echocardiography. We determined cardiomyocyte enlargement and proliferation using microscopy techniques on myocardial tissue and isolated cardiomyocytes from a separate sample of 55 humans without known systemic or history of heart disease (age range 1 day-68 years). Using the data about myocardial growth and cardiomyocyte enlargement and proliferation, we developed a model for assessing how both cellular mechanisms contribute to myocardial growth. Between newborns and adults, the number of cardiomyocytes in the LV increased 3.6-fold from 1.3 × 109 to 4.7 × 109. Mitotic cardiomyocytes were detected at low level throughout life with the highest rate of 0.044% during the first year of life and decreased to turnover levels above the age of 20 years. The cell cycle activity was associated with an increase in cardiomyocyte number and an increase in cardiomyocyte DNA content, leading to polyploidy. During post-natal heart growth, the mean cardiomyocyte volume grew 13-fold from 3,496 µm3 in newborns to 47,073 µm3 in adults. Combining our results in a model showed that proliferation contributed 37% and enlargement 63% of the cardiomyocyte-dependent mechanisms of post-natal myocardial growth. In summary, physiologic heart growth in humans relies on both cardiomyocyte proliferation and enlargement, with proliferation playing a substantial role in infants and during a second growth spurt in teenagers.
- © 2011 by American Heart Association, Inc.