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Critical Care and Respiratory Divisions, Royal Victoria Hospital, and Meakins-Christie Laboratories, McGill University, Montreal, Quebec H3A 1A1, Canada
In this study, we assessed
the effects of in vivo hypoxia on the expression of Tie-2 receptors and
angiopoietins in various organs of conscious rats and correlated these
effects with the expression of hypoxia-inducible factor-1 (HIF-1).
RT-PCR and Southern blotting were used to amplify mRNA expression of
angiopoietin-1, -2, and -3, Tie-2, and HIF-1
in tissues of normoxic
and hypoxic (fraction of inspired oxygen of 9-10% for either 12 or 48 h) rats. Hypoxia provoked a decline in angiopoietin-1 mRNA
and Tie-2 mRNA, protein, and phosphorylation levels in the lung, liver,
cerebellum, and heart but not in the kidney and diaphragm. In
comparison, hypoxia raised the levels of angiopoietin-2 mRNA in the
cerebellum and angiopoietin-3 mRNA in the lung, kidney, and diaphragm.
HIF-1 mRNA was abundant in most organs of normoxic rats but was
significantly induced in the kidney and diaphragm of hypoxic
rats. We conclude that in vivo hypoxia exerts inhibitory effects on the
activity of the angiopoietin-1/Tie-2 receptor pathway through reduction of angiopoietin-1 and upregulation of angiopoietin-2 and -3. Induction of angiopoietin-3 in the kidney and diaphragm of hypoxic rats could be
mediated through the HIF-1 transcription factor.
angiogenesis; TEK receptors
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