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J Appl Physiol (May 17, 2002). doi:10.1152/japplphysiol.00318.2002
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Articles in PresS, published online ahead of print May 17, 2002
J Appl Physiol, 10.1152/jap.00318.2002
Submitted on April 10, 2002
Accepted on May 13, 2002

Angiopoietin-2 and rat brain capillary remodeling during adaptation and de-adaptation to prolonged mild hypoxia

Paola Pichiule1 and Joseph C LaManna1*

1 Department of Anatomy, Case Western Reserve University, Cleveland, Ohio, USA

* To whom correspondence should be addressed. E-mail: jcl4{at}po.cwru.edu.

Angiogenesis is a crucial component of rat brain adaptation to prolonged hypoxia, but it is not known whether this structural change is permanent or reversed upon return to normoxia. Also, the intrinsic mechanisms controlling brain microvascular plasticity in response to oxygen availability remains unclear. Our results indicate that capillary density in the rat cerebral cortex increased by 60% after 3w of hypoxia and it progressively decreased to pre-hypoxic values after 3w of normoxic recovery (de-adaptation). Ang2 expression in the capillary endothelium was induced between 6h and 14d of hypoxia but fell to control levels at 21d of hypoxia. During de-adaptation, Ang2 levels were elevated at 1 to 14d but decreased to baseline at 21d. In contrast, the constitutive expression of Ang1 and Tie2 was not affected during hypoxia or de-adaptation. TUNEL-positive endothelial cells and caspase-3 activation were observed at 7 and 14d of de-adaptation. These data suggest that Ang2 might modulate both angiogenesis and vascular regression in the rat brain and that capillary regression occurring during de-adaptation involves activation of apoptosis.




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