The role of androgens on hypoxia-inducible factor (HIF)-1α-induced angiogenesis and on the survival of ischemically challenged skin flaps in a rat model
Version of Record online: 18 JUN 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 32, Issue 6, pages 475–481, September 2012
How to Cite
Shafighi, M., Olariu, R., Brun, C., Fathi, A. R., Djafarzadeh, S., Jakob, S. M., Hunger, R. E., Banic, A. and Constantinescu, M. A. (2012), The role of androgens on hypoxia-inducible factor (HIF)-1α-induced angiogenesis and on the survival of ischemically challenged skin flaps in a rat model. Microsurgery, 32: 475–481. doi: 10.1002/micr.21996
- Issue online: 5 SEP 2012
- Version of Record online: 18 JUN 2012
- Manuscript Accepted: 4 APR 2012
- Manuscript Received: 7 DEC 2011
- Departmental funds
Effects of androgens on angiogenesis are controversial. Hypoxia-inducible factor (HIF)-1α promotes expression of vascular endothelial growth factor (VEGF) that stimulates angiogenesis.
This study investigates whether androgens stabilize HIF-1α in endothelial cells, and androgen depletion decreases VEGF concentrations and skin flap survival.
Materials and Methods:
Male human umbilical vein endothelial cells (HUVECs) were exposed to dihydrotestosterone (DHT) and HIF-1α expression was measured. In male Wistar rats, standardized proximally based random pattern dorsal skin flaps (3 × 9 cm) were raised 4 weeks after orchiectomy and sham operation, respectively (n = 10, each). Flap VEGF concentrations (immunohistochemistry), perfusion (Laser Doppler), and viability (digital planimetry) were measured.
DHT induced HIF-1α expression in HUVECs. Androgen depletion induced decreased VEGF expression (P = 0.003), flap perfusion (P < 0.05), and survival (44.4% ± 5.2%) compared to controls (35.5% ± 4.5%; P = 0.003).
In vitro, androgens may stimulate HIF-1α under normoxic conditions. In rats, androgen depletion decrease VEGF expression and flap survival. © 2012 Wiley Periodicals, Inc. Microsurgery 2012.