Short-term hypoxia/reoxygenation activates the angiogenic pathway in rat caudate putamen.
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Date
2013-06
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Abstract
In response to hypoxia, tissues have to implement numerous mechanisms to enhance oxygen delivery, including the
activation of angiogenesis. This work investigates the angiogenic response of the hypoxic caudate putamen after
several recovery times.
Adult Wistar rats were submitted to acute hypoxia and analysed after 0 h, 24 h and 5 days of reoxygenation.
Expression of hypoxia-inducible factor-1 alfa (HIF-1α) and angiogenesis-related genes including vascular endothelial
growth factor (VEGF), adrenomedullin (ADM) and transforming growth factor-beta 1 (TGF-β1) was determined by
both RT-PCR and ELISA. For vessel labelling, lectin location and expression were analysed using histochemical and
image processing techniques (fractal dimension).
Expression of Hif-1α, Vegf, Adm and Tgf-β1 mRNA rose immediately after hypoxia and this increase persisted in
some cases after 5 days post-hypoxia. While VEGF and TGF-β1 protein levels increased parallel to mRNA
expression, ADM remained unaltered. The quantification of the striatal vessel network showed a significant augmentation
at 24 h of reoxygenation.
These results reveal that not only short-term hypoxia, but also the subsequent reoxygenation period, up-regulate the
angiogenic pathway in the rat caudate putamen as a neuroprotective mechanism to hypoxia that seeks to maintain a
proper blood supply to the hypoxic tissue, thereby minimizing the adverse effects of oxygen deprivation.
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Keywords
Adrenomedullin, angiogenesis, hypoxia, hypoxia-inducible factor, reoxygenation, vascular endothelial growth factor
Citation
Molina F, Rus A, Peinado M A, Moral M L del. Short-term hypoxia/reoxygenation activates the angiogenic pathway in rat caudate putamen. Journal of Biosciences. 2013 June; 38(2): 363-371.