Redirecting cardiac growth mechanisms for therapeutic regeneration
Ravi Karra, Kenneth D. Poss
Ravi Karra, Kenneth D. Poss
Published February 1, 2017
Citation Information: J Clin Invest. 2017;127(2):427-436. https://doi.org/10.1172/JCI89786.
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Redirecting cardiac growth mechanisms for therapeutic regeneration

Abstract

Heart failure is a major source of morbidity and mortality. Replacing lost myocardium with new tissue is a major goal of regenerative medicine. Unlike adult mammals, zebrafish and neonatal mice are capable of heart regeneration following cardiac injury. In both contexts, the regenerative program echoes molecular and cellular events that occur during cardiac development and morphogenesis, notably muscle creation through division of cardiomyocytes. Based on studies over the past decade, it is now accepted that the adult mammalian heart undergoes a low grade of cardiomyocyte turnover. Recent data suggest that this cardiomyocyte turnover can be augmented in the adult mammalian heart by redeployment of developmental factors. These findings and others suggest that stimulating endogenous regenerative responses can emerge as a therapeutic strategy for human cardiovascular disease.

Authors

Ravi Karra, Kenneth D. Poss

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Figure 1

Modes of cardiomyocyte growth.

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Modes of cardiomyocyte growth. (A) During cardiac development, cardiac g...
(A) During cardiac development, cardiac growth occurs through addition of new cardiomyocytes via progenitor cell differentiation (top) followed by hyperplastic growth (bottom). Undifferentiated progenitor cells give rise to cardiac progenitors at the heart tube stage, followed by hyperplastic proliferation of cardiomyocytes during the remainder of development. (B) In contrast, the adult mammalian heart grows predominantly by either physiologic hypertrophy (top) or pathologic hypertrophy (bottom). With physiologic hypertrophy, the heart uniformly enlarges without organ fibrosis. Pathologic hypertrophy occurs after injury and is marked by fibrosis and heterogeneous cellular hypertrophy.