A more recent version of this article appeared on April 13, 2001

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(Circulation Research. 2001;0:hh0701.089753.)
© 2001 American Heart Association, Inc.

Online First Article

Adaptive Mechanisms That Preserve Cardiac Function in Mice Without Myoglobin

Annette P. Meeson, Nina Radford, John M. Shelton, Pradeep P. A. Mammen, J. Michael DiMaio, Kelley Hutcheson, Yanfeng Kong, Joel Elterman, R. Sanders Williams Daniel J. Garry

From the Departments of Internal Medicine (A.P.M., N.R., J.M.S., P.P.A.M., Y.K., J.E., R.S.W., D.J.G.), Thoracic and Cardiovascular Surgery (J.M.D., K.H.), and Molecular Biology (R.S.W., D.J.G.), University of Texas Southwestern Medical Center, Dallas.

Correspondence to Daniel J. Garry, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., NB11.200, Dallas, TX 75390-8573. E-mail garry{at}ryburn.swmed.edu

Abstract

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 1 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.

Key Words: myoglobin • transgenic mice • metabolism • hypoxia • vasculature

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