Cardiomyogenesis in the Aging and Failing Human Heart
Background—Two opposite views of cardiac growth are currently held: one views the heart as a static organ, characterized by a large number of cardiomyocytes, which are present at birth and live as long as the organism; and the other views the heart a highly plastic organ in which the myocyte compartment is restored several times during the course of life.
Methods and Results—The average age of cardiomyocytes, vascular endothelial cells (ECs), and fibroblasts and their turnover rates were measured by retrospective 14C birth dating of cells in 19 normal hearts, 2 to 78 years of age, and in 17 explanted failing hearts, 22 to 70 years of age. We report that the human heart is characterized by a significant turnover of ventricular myocytes, ECs, and fibroblasts, physiologically and pathologically. Myocyte, EC, and fibroblast renewal is very high shortly after birth, decreases during postnatal maturation, remains relatively constant in the adult organ, and increases dramatically with age. From 20 to 78 years of age, the adult human heart replaces entirely its myocyte, EC, and fibroblast compartment ~8, ~6, and ~8 times, respectively. Myocyte, EC, and fibroblast regeneration is further enhanced with chronic heart failure (CHF).
Conclusions—The human heart is a highly dynamic organ that retains a remarkable degree of plasticity throughout life and in the presence of CHF. However, the ability to regenerate cardiomyocytes, vascular ECs, and fibroblasts cannot prevent the manifestations of myocardial aging or oppose the negative effects of ischemic and idiopathic dilated cardiomyopathy.
- Received May 15, 2012.
- Accepted August 8, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited