title: Adaptive mechanisms that preserve cardiac function in mice without myoglobin.
abstract: Mice lacking myoglobin survive to adulthood and meet the circulatory demands of exercise and pregnancy without cardiac decompensation. In the present study, we show that many myoglobin-deficient embryos die in utero at midgestation with signs of cardiac failure. Fetal mice that survive to gestational day 12.5, however, suffer no subsequent excess mortality. Survival in the absence of myoglobin is associated with increased vascularity and the induction of genes encoding the hypoxia-inducible transcription factors 1alpha and 2, stress proteins such as heat shock protein 27, and vascular endothelial growth factor. These adaptations are evident in late fetal life, persist into adulthood, and are sufficient to maintain normal myocardial oxygen consumption during stressed conditions. These data reveal that myoglobin is necessary to support cardiac function during development, but adaptive responses evoked in some animals can fully compensate for the defect in cellular oxygen transport resulting from the loss of myoglobin.
authors: Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors: A P
authors: AP
authors: Meeson
authors: N
authors: N
authors: Radford
authors: J M
authors: JM
authors: Shelton
authors: P P
authors: PP
authors: Mammen
authors: J M
authors: JM
authors: DiMaio
authors: K
authors: K
authors: Hutcheson
authors: Y
authors: Y
authors: Kong
authors: J
authors: J
authors: Elterman
authors: R S
authors: RS
authors: Williams
authors: D J
authors: DJ
authors: Garry
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001808:Blood Vessels / Q000002:abnormalities / Q000473:pathology; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D020964:Embryo Loss / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004622:Embryo, Mammalian / Q000473:pathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006333:Heart Failure / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D066298:In Vitro Techniques; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000235:genetics / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009211:Myoglobin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D010101:Oxygen Consumption / Q000235:genetics; D010641:Phenotype; D015996:Survival Rate; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; D006360:Heat-Shock Proteins; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines; D009211:Myoglobin; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000099162:Endothelial PAS Domain-Containing Protein 1; C497443:Hif1a protein, mouse