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Prevention of skin flap necrosis by estradiol involves reperfusion of a protected vascular network.
- Source :
-
Circulation research [Circ Res] 2009 Jan 30; Vol. 104 (2), pp. 245-54, 12p following 254. Date of Electronic Publication: 2008 Dec 04. - Publication Year :
- 2009
-
Abstract
- Although 17beta-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 (ERalpha(-/-)) but maintained in chimeric mice reconstituted with ERalpha-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.
- Subjects :
- Animals
Bone Marrow Transplantation
Cell Survival
Dermatologic Surgical Procedures
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Implants
Estradiol administration & dosage
Estrogen Receptor alpha genetics
Estrogen Receptor alpha metabolism
Female
Ischemia etiology
Ischemia metabolism
Ischemia pathology
Ischemia physiopathology
Mice
Mice, Hairless
Mice, Inbred C57BL
Mice, Knockout
Mice, Nude
Necrosis
Ovariectomy
Regional Blood Flow
Selective Estrogen Receptor Modulators pharmacology
Skin pathology
Tamoxifen pharmacology
Time Factors
Estradiol metabolism
Ischemia prevention & control
Skin blood supply
Skin metabolism
Surgical Flaps adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4571
- Volume :
- 104
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Circulation research
- Publication Type :
- Academic Journal
- Accession number :
- 19059842
- Full Text :
- https://doi.org/10.1161/CIRCRESAHA.108.182410