title: Early origins of cardiac hypertrophy: does cardiomyocyte attrition programme for pathological 'catch-up' growth of the heart?
abstract: 1. Epidemiological and experimental evidence suggests that adult development of cardiovascular disease is influenced by events of prenatal and early postnatal life. Cardiac hypertrophy is recognized as an important predictor of cardiovascular morbidity and mortality, but the developmental origins of this condition are not well understood. 2. In the heart, a switch from hyperplastic to hypertrophic cellular growth occurs during late prenatal or early postnatal life. Postnatal growth of the heart is almost entirely reliant on hypertrophy of individual cardiomyocytes, and damage to heart muscle in adulthood is typically not reparable by cell replacement. Therefore, a reduced number of cardiomyocytes may render the heart more vulnerable in situations where an increased workload is required. 3. A number of different animal models have been used to study fetal programming of adult diseases, including nutritional, hypoxic, maternal/neonatal endocrine stress and genetic models. Although studies investigating the cellular basis of myocardial disease in growth-restricted models are limited, a reduction in cardiomyocyte number through either reduced cellular proliferation or increased apoptosis appears to be a central feature. 4. The mechanisms responsible for the programming of adult cardiovascular disease are poorly understood. We hypothesize that cardiac hypertrophy can have a developmental origin in excess cardiomyocyte attrition during a critical perinatal growth window. Findings that have directly assessed the impact of fetal growth restriction on the myocardium are considered and cellular and molecular mechanisms involved in the potential pathological 'catch-up' growth of the heart during later maturation are identified.
authors.affiliation: Department of Physiology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Enzo R
authors.initials: ER
authors.lastname: Porrello
authors.forename: Robert E
authors.initials: RE
authors.lastname: Widdop
authors.forename: Lea M D
authors.initials: LM
authors.lastname: Delbridge