Fetal Origins of Cardiovascular Disease

Audra      Wise; Shumei      Yang; Lubo      Zhang

Abstract

Human epidemiological studies have shown a clear association of adverse intrauterine environment and an increased risk of ischemic heart disease in later adult life. Although adult lifestyle adds to the effects developed during intrauterine life, compelling evidence indicates that the association of ischemic heart disease with adverse intrauterine environment does not reflect confounding variables linked to adult lifestyle. It is suggested that epigenetic programming in the gene expression pattern caused by adverse intrauterine environments at a critical period of development in early life plays an important role in the heart development, and its lifelong pathophysiological consequences in the adult heart. Potential fetal programming of adult disease has been shown in maternal undernutrition and fetal exposure to glucocorticoids, hypoxia, alcohol, tobacco smoking, and cocaine. Although early epidemiological studies suggest that small body size at birth is associated with an increased risk of death from ischemic heart disease in the adult, it is becoming clear that fetal growth restriction is not a prerequisite of adult disease. Recent animal studies suggest that adverse intrauterine environments suppress fetal cardiac function, alter cardiac gene expression pattern, increase apoptosis of cardiomyocytes, cause a premature exit of the cell cycle of cardiomyocytes and myocyte hypertrophy, and result in an increase in susceptibility of the adult heart to ischemia-reperfusion injury. This review discusses recent epidemiological evidence in humans, as well as evidence from studies in experimental animals, of an association of adverse intrauterine environments and an increased risk of ischemic heart disease in the adult, and the possible molecular mechanisms of epigenetic programming involved in fetal gene expression pattern, which is essential in explaining many fundamental biological processes by which a variety of cardiovascular dysfunctions and disease emerge and evolve.

Keywords: Maternal undernutrition, Corticosteroid, Fetal anemia, abused substances, mitogen-activated protein kinase (MAPK)