Role of Hypoxia in the Evolution and Development of the Cardiovascular System

Abstract

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 O 2 delivery to allow understanding of adaptive responses to O 2 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 O 2 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.

Development of cardiac form and function in ectothermic sauropsids

“…Perhaps reflecting the fundamental importance of the heart, the study of cardiac form and function in particular has been the subject of studies for comparative morphologists and physiologists for centuries (Bojanus, 1819;Panizza, 1833). As adults, reptiles represent a distinctive cardiovascular transition between the single circulation of fishes and the double circulation with systemic and pulmonary circuits of birds and mammals (e.g., White, 1968;1970;Burggren, 1978;Johansen and Burggren, 1985;Wang et al, 1998;Hicks, 2002;Fisher and Burggren, 2007). Briefly, turtles, non-varanid lizards and snakes possess two separate atria that eject blood into ventricular chamber consisting of the cavum pulmonale, cavum venosum, and cavum arteriosum.…”

Spermidine/Spermine-N1-Acetyltransferase 2 Is an Essential Component of the Ubiquitin Ligase Complex That Regulates Hypoxia-inducible Factor 1α

“…Oxygen homeostasis represents a critical organizing principle of metazoan evolution and biology (1,2). Hypoxia-inducible factor 1 (HIF-1) 2 functions as a master regulator of oxygen homeostasis in metazoan species as diverse as Caenorhabditis elegans, an organism of Ͻ10 3 cells with no specialized systems for O 2 delivery, to Homo sapiens, an organism with complex respiratory and circulatory systems to capture O 2 and deliver it to each of Ͼ10 13 cells (1,(3)(4)(5)(6)(7).…”

“…Hypoxia-inducible factor 1 (HIF-1) 2 functions as a master regulator of oxygen homeostasis in metazoan species as diverse as Caenorhabditis elegans, an organism of Ͻ10 3 cells with no specialized systems for O 2 delivery, to Homo sapiens, an organism with complex respiratory and circulatory systems to capture O 2 and deliver it to each of Ͼ10 13 cells (1,(3)(4)(5)(6)(7). Precise moment-to-moment matching of O 2 supply and demand is required for maintenance of cellular energetics and redox equilibrium that in turn is necessary for the survival of individual cells and of the organism (2, 8).…”

“…Section 1734 solely to indicate this fact. 1 hydroxylation of Asn 803 by factor inhibiting HIF-1 (36,37), which binds to HIF-1␣ and to VHL (38). Factor inhibiting HIF-1 and OS-9 were identified in a yeast two-hybrid screen for human proteins that interact with amino acid residues 576 -826 of HIF-1␣ (34,38).…”

Cardio-respiratory development in bird embryos: new insights from a venerable animal model

“…These approaches are often combined with exposure of the developing embryo to hypoxia or hypercapnia as stressors on the cardiovascular, respiratory, and acidbase balance systems to tease apart elements of cardiorespiratory physiological control (Adair et al, 1987;Strick et al, 1991;Burton and Palmer, 1992;Rouwet et al, 2002;Crossley et al, 2003a;Villamor et al, 2004;Fisher and Burggren, 2007;Copeland and Dzialowski, 2009;Lindgren and Altimiras, 2009;Acosta and Hernandez, 2012;Zhang and Burggren, 2012;Mueller et al, 2013b;Andrewartha et al, 2014;Mueller et al, 2014b;Burggren et al, 2015b;Jonker et al, 2015;Itani et al, 2016). …”