Published online before print December 4, 2008, doi: 10.1161/CIRCRESAHA.108.182410
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Submitted on October 5, 2007
Revised on October 28, 2008
Accepted on November 21, 2008
Prevention of Skin Flap Necrosis by Estradiol Involves Reperfusion of a Protected Vascular Network
Céline E. Toutain ;
From Institut National de la Santé et de la Recherche Médicale (C.E.T., L.B., H.B., J.F., M.-J.F., P.G., J.-F.A., F.L.), U858, Institut de Médecine Moléculaire de Rangueil, IFR31 Toulouse; Université Toulouse III Paul-Sabatier (C.E.T., H.B., J.F., M.-J.F., P.G., J.-F.A., F.L.); Departement d'Anatomie-Pathologique (I.R.-L.), Ecole Nationale Vétérinaire de Toulouse; Laboratoire des Laboratoire des Intéractions Moléculaires et Réactivité Chimique et Photochimique (P.V.), Unité Mixte de Recherche 5623 au Centre National de la Recherche Scientifique, Université Paul Sabatier, Toulouse; Institut de Génétique et de Biologie Moléculaire et Cellulaire (Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université Louis Pasteur, Collège de France) (A.K., P.C.) and Institut Clinique de la Souris, Illkirch; 7 Centre de Recherche sur la Peau (A.-M.S.), Pierre Fabre Dermocosmétique, Toulouse; and Explorations Fonctionnelles Physiologiques (J.-F.A.), CHU Toulouse-Rangueil, France.
* To whom correspondence should be addressed. E-mail: Francoise.Lenfant{at}inserm.fr.
Although 17
-estradiol (E2) is protective in experimental models of myocardial and brain ischemia, its effect on skin ischemia remains unknown. Here, we assessed the protective effect of E2 in a mouse model of skin ischemia, mimicking the surgery of skin flaps. Whereas necrosis appeared in the half portion of the skin flap within 1 week after surgery in ovariectomized mice, it was reduced up to 10-fold when mice were pretreated with E2, at least 3 days before the surgery. The beneficial effect of E2 appeared to be attributable to an increase in skin survival, revealed by measuring viability of ex vivo explants and enhancement of the antiapoptotic Bcl-2 protein expression in vivo. This protective effect on the skin contributed to the protection of the vascular network and facilitated reperfusion, which was found to be accelerated in ovariectomized E2-treated mice, whereas hemorrhages were observed in untreated mice. E2 also increased expression of fibroblast growth factor-2 isoforms in the skin and circulating vascular endothelial growth factor in the serum. Finally, this protective effect of E2 was abolished in estrogen receptor–deficient mice (ER
-/-) but maintained in chimeric mice reconstituted with ER-deficient bone marrow, indicating dispensable action of E2 in bone marrow–derived cells. This protective effect of E2 was mimicked by treatment with tamoxifen, a selective estrogen receptor modulator. In conclusion, we have demonstrated for the first time that E2 exerts a major preventive effect of skin flap necrosis through a prevention of ischemic-induced skin lesions, including those of the vascular network, which contributes to accelerate the reperfusion of the skin flap.
Key words: estradiol • skin flap model • ischemia
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Circ. Res. 2009 104: 135-137.[Extract] [Full Text] [PDF]
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