Role of hypoxia in the evolution and development of the cardiovascular system.

How multicellular organisms obtain and use oxygen and other substrates has evolved over hundreds of millions of years in parallel with the evolution of oxygen-delivery systems. A steady supply of oxygen is critical to the existence of organisms that depend on oxygen as a primary source of fuel (i.e., those that live by aerobic metabolism). Not surprisingly, a number of mechanisms have evolved to defend against oxygen deprivation. This review highlights evolutionary and developmental aspects of O2 delivery to allow understanding of adaptive responses to O2 deprivation (hypoxia). First, we consider how the drive for more efficient oxygen delivery from the heart to the periphery may have shaped the evolution of the cardiovascular system, with particular attention to the routing of oxygenated and deoxygenated blood in the cardiac outlet. Then we consider the role of O2 in the morphogenesis of the cardiovascular system of animals of increasing size and complexity. We conclude by suggesting areas for future research regarding the role of oxygen deprivation and oxidative stress in the normal development of the heart and vasculature or in the pathogenesis of congenital heart defects.