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Angiogenesis is VEGF-independent in the aged striatum of male rats exposed to acute hypoxia

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Abstract

Brain hypoxia is involved in many diseases. The activation of angiogenesis is one of the major adaptive mechanisms to counteract the adverse effects of hypoxia. In a previous work, we have shown that the adult rat striatum promotes angiogenesis in response to hypoxia via upregulation of the most important proangiogenic factor, the vascular endothelial growth factor (VEGF). However, the effects of hypoxia on angiogenesis in the aged striatum remain unknown and constitute our aim. Here we show the upregulation of hypoxia-inducible factor-1α in the striatum of aged (24–25 months old) Wistar rats exposed to acute hypoxia and analysed during a reoxygenation period ranging from 0 h to 5 days. While the mRNA expression of the proangiogenic factors VEGF, transforming growth factor-β1 (TGF-β1), and adrenomedullin dropped at 0 h post-hypoxia compared to normoxic control, no changes were detected at the protein level, showing an impaired response of these proangiogenic factors to hypoxia in the aged striatum. However, the striatal blood vessel network increased at 24 h of reoxygenation, suggesting that mechanisms independent from these proangiogenic factors may be involved in hypoxia-induced angiogenesis in the striatum of aged rats. A thorough understanding of the factors involved in the response to hypoxia is essential to guide the design of therapies for hypoxia-related diseases in the aged brain.

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Acknowledgements

We wish to thank to Dr. Rafael Lomas for his statistic assistance, and to Dra. M. Rosario Sepúlveda for critical reading of the manuscript.

Funding

This study was funded by Instituto de Salud Carlos III (PI081222) and University of Jaén (RFC/PP2008/UJA_08_16_20).

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Authors and Affiliations

  1. Department of Health Science, University of Jaén, Paraje Las Lagunillas s/n, 23071, Jaén, Spain

    Francisco Molina

  2. Department of Experimental Biology, University of Jaén, Paraje Las Lagunillas s/n, 23071, Jaén, Spain

    M. Luisa del Moral & M. Ángeles Peinado

  3. Department of Cell Biology, University of Granada, Avenida de la Fuentenueva s/n, 18071, Granada, Spain

    Alma Rus

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  1. Francisco Molina
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  2. M. Luisa del Moral
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  4. Alma Rus
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Correspondence to Alma Rus.

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Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in animals were in accordance with the ethical standards of the University of Jaén (Spain) at which the study was conducted.

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Molina, F., del Moral, M.L., Peinado, M.Á. et al. Angiogenesis is VEGF-independent in the aged striatum of male rats exposed to acute hypoxia. Biogerontology 18, 759–768 (2017). https://doi.org/10.1007/s10522-017-9709-5

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  • DOI: https://doi.org/10.1007/s10522-017-9709-5

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