Transgenic mice expressing constitutively active HIF-1α in epidermis displayed a 66% increase in dermal capillaries and a 13-fold elevation of VEGF expression without inducing edema or leakage.
HIF-1alpha overexpression induces functional hypervascularity without the adverse effects of vascular leakage or inflammation seen with direct VEGF overexpression, highlighting its potential for treating tissue ischemia.
Hypoxia-inducible factor-1alpha (HIF-1alpha) transactivates genes required for energy metabolism and tissue perfusion and is necessary for embryonic development and tumor explant growth. HIF-1alpha is overexpressed during carcinogenesis, myocardial infarction, and wound healing; however, the biological consequences of HIF-1alpha overexpression are unknown. Here, transgenic mice expressing constitutively active HIF-1alpha in epidermis displayed a 66% increase in dermal capillaries, a 13-fold elevation of total vascular endothelial growth factor (VEGF) expression, and a six- to ninefold induction of each VEGF isoform. Despite marked induction of hypervascularity, HIF-1alpha did not induce edema, inflammation, or vascular leakage, phenotypes developing in transgenic mice overexpressing VEGF cDNA in skin. Remarkably, blood vessel leakage resistance induced by HIF-1alpha overexpression was not caused by up-regulation of angiopoietin-1 or angiopoietin-2. Hypervascularity induced by HIF-1alpha could improve therapy of tissue ischemia.
Elson et al. (Mon,) reported a other. Constitutively active HIF-1α overexpression in epidermis was evaluated on Dermal capillaries and VEGF expression. Transgenic mice expressing constitutively active HIF-1α in epidermis displayed a 66% increase in dermal capillaries and a 13-fold elevation of VEGF expression without inducing edema or leakage.