Hypoxia and Fetal Heart Development

A.      J. Patterson; L.      Zhang

doi:10.2174/156652410792630643

Abstract

Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although “normal” hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes fetal programming of abnormality in the hearts development. The altered expression pattern of cardioprotective genes such as protein kinase c epsilon, heat shock protein 70, and endothelial nitric oxide synthase, likely predisposes the developing heart to increased vulnerability to ischemia and reperfusion injury later in life. The events underlying the long-term changes in gene expression are not clear, but likely involve variation in epigenetic regulation.

Keywords: Hypoxia, fetal heart, development, fetal programming, Electron transport chain, Cardiogenesis, Glycolytic flux, Hypoxia inducible factor 1, Vascular endothelial growth factor, Angiogenesis, Vasculogenesis, Angioblasts, Vascular plexus, Myocardium, Cardiomyocyte, Hemodynamic stress, Nitroimadazole compounds, Pimonidazole, Nitroreductases, Embryogenesis, Tumorigenesis, Apoptosis, Cardiac troponin T, VEGF, HIF family, Erythropoiesis, Catecholamines, Calcium homeostasis, Myocardial infarction, Cardioprotective genes, PKCe, Epigenetics, Cocaine, Vasoconstrictor, Reactive oxygen species, Homeostasis, HSP70