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Hypoxic Induction of Myocardial Vascularization During Development

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Hypoxia

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 543))

Abstract

The development of the heart is closely linked to its temporally and spatially regulated vascularization. Hypoxia has been shown to stimulate myocardial capillary growth and improve myocardial perfusion during reperfusion in postnatal animals exposed to chronic or intermittent exposure to hypobaria. Vascular endothelial growth factor (VEGF) is up-regulated by hypoxia via HIF-1α, and these two molecules are colocalized with presumptive regions of hypoxia. VEGF up-regulation in embryonic and fetal hearts correlates with vascular tube formation which progresses from an epicardial to endocardial direction prior to the establishment of a functional coronary circulation. Our studies on explanted embryonic quail hearts indicate that vascular tube formation is enhanced by hypoxia (5–10% O2) and inhibited by hyperoxia. Three splice variants of VEGF (122, 126, 190) were found to increase and decrease with hypoxia and hyperoxia, respectively. While VEGF synthesis is stimulated by hypoxia, there are differences in the vascular patterning between exogenous VEGF-induced vascularization and that induced by hypoxia. Thus, other, yet to be identified, molecules are recruited by hypoxia. Acute hypoxia selectively enhances at least three splice variants of VEGF-A, and also selectively up-regulates VEGFR-1 (flt-1). However, we suggest that VEGF-B, a ligand for VEGFR-1 may contribute to embryonic myocardial vascularization, since we have shown that it plays a key role in this process under normoxic conditions. A second mechanism by which hypoxia may play a role in vascularization of the heart is via its vasodilatory effects, once the coronary circulation is functional. Increased blood flow serves as a mechanical (stretch) trigger for activation of VEGF and its receptors. In sum, there is evidence that a relative hypoxia provides both metabolic and mechanical stimuli for vascular growth in the developing heart.

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Authors
  1. Robert J. Tomanek
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  2. Donald D. Lund
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  3. Xinping Yue
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Editor information

Editors and Affiliations

  1. Colorado Center for Altitude Medicine and Physiology, University of Colorado Health Sciences Center, Denver, Colorado, USA

    Robert C. Roach  & Peter H. Hackett (President) &  (President)

  2. University of California, San Diego, La Jolla, California, USA

    Peter D. Wagner

  3. International Society for Mountain Medicine, Ridgway, Colorado, USA

    Peter H. Hackett (President) (President)

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© 2003 Springer Science+Business Media New York

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Tomanek, R.J., Lund, D.D., Yue, X. (2003). Hypoxic Induction of Myocardial Vascularization During Development. In: Roach, R.C., Wagner, P.D., Hackett, P.H. (eds) Hypoxia. Advances in Experimental Medicine and Biology, vol 543. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8997-0_10

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  • DOI: https://doi.org/10.1007/978-1-4419-8997-0_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4753-8

  • Online ISBN: 978-1-4419-8997-0

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