Cardiomyocyte proliferation contributes to heart growth in young humans

被引:556
作者
Mollova, Mariya [1 ,3 ]
Bersell, Kevin [1 ,5 ,6 ]
Walsh, Stuart [1 ,3 ]
Savla, Jainy [1 ,5 ]
Das, Lala Tanmoy [1 ]
Park, Shin-Young [2 ,3 ]
Silberstein, Leslie E. [2 ,4 ]
dos Remedios, Cristobal G. [7 ]
Graham, Dionne [1 ,3 ]
Colan, Steven [1 ,3 ]
Kuehn, Bernhard [1 ,3 ,8 ,9 ]
机构
[1] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA
[2] Boston Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[5] Boston Univ, Sch Med, Boston, MA 02118 USA
[6] Vanderbilt Univ, Dept Pharmacol, Sch Med, Nashville, TN 37232 USA
[7] Univ Sydney, Dept Anat, Bosch Inst, Sydney, NSW 2006, Australia
[8] Harvard Stem Cell Inst, Cambridge, MA 02138 USA
[9] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA
关键词
heart failure; pediatrics; CARDIAC STEM-CELLS; ISCHEMIC CARDIOMYOPATHY; REGENERATION; HYPERPLASIA; CHILDREN; MYOCYTES; CARDIOMYOGENESIS; HYPERTROPHY; MYOCARDIUM; NUCLEI;
D O I
10.1073/pnas.1214608110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1446 / 1451
页数:6
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