Cardiomyocyte Proliferation from Fetal- to Adult- and from Normal- to Hypertrophy and Failing Hearts

SIMPLE SUMMARY: Death from injury to the heart from a variety of causes remains a major cause of mortality worldwide. The cardiomyocyte, the major contracting cell of the heart, is responsible for pumping blood to the rest of the body. During fetal development, these immature cardiomyocytes are small and rapidly divide to complete development of the heart by birth when they develop structural and functional characteristics of mature cells which prevent further division. All further growth of the heart after birth is due to an increase in the size of cardiomyocytes, hypertrophy. Following the loss of functional cardiomyocytes due to coronary artery occlusion or other causes, the heart is unable to replace the lost cells. One of the significant research goals has been to induce adult cardiomyocytes to reactivate the cell cycle and repair cardiac injury. This review explores the developmental, structural, and functional changes of the growing cardiomyocyte, and particularly the sarcomere, responsible for force generation, from the early fetal period of reproductive cell growth through the neonatal period and on to adulthood, as well as during pathological response to different forms of myocardial diseases or injury. Multiple issues relative to cardiomyocyte cell-cycle regulation in normal or diseased conditions are discussed. ABSTRACT: The cardiomyocyte undergoes dramatic changes in structure, metabolism, and function from the early fetal stage of hyperplastic cell growth, through birth and the conversion to hypertrophic cell growth, continuing to the adult stage and responding to various forms of stress on the myocardium, often leading to myocardial failure. The fetal cell with incompletely formed sarcomeres and other cellular and extracellular components is actively undergoing mitosis, organelle dispersion, and formation of daughter cells. In the first few days of neonatal life, the heart is able to repair fully from injury, but not after conversion to hypertrophic growth. Structural and metabolic changes occur following conversion to hypertrophic growth which forms a barrier to further cardiomyocyte division, though interstitial components continue dividing to keep pace with cardiac growth. Both intra- and extracellular structural changes occur in the stressed myocardium which together with hemodynamic alterations lead to metabolic and functional alterations of myocardial failure. This review probes some of the questions regarding conditions that regulate normal and pathologic growth of the heart.