Tamoxifen and estrogen attenuate enhanced vascular reactivity induced by estrogen deficiency in rat carotid arteries

Tsang, Suk Ying; Yao, Xiaoqiang; Chan, Hoi Yun; Chan, F.H.Y.; Leung, Cecilia S.; Yung, Lai Ming; Au, Chak Leung; Chen, Zhenyu; Laher, Ismail; Huang, Yü

doi:10.1016/j.bcp.2006.12.022

Cited by 7 publications

(7 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…http://circres.ahajournals.org/ Downloaded from modulator confers estrogenic effect in various vascular systems 43,44 are in agreement with the vascular protection evidenced in the present model. In summary, we demonstrated here for the first time that a short administration of E2 prevents ischemia-induced skin necrosis.…”

Section: Circulation Research January 30 2009supporting

confidence: 92%

See 1 more Smart Citation

Prevention of Skin Flap Necrosis by Estradiol Involves Reperfusion of a Protected Vascular Network

Toutain

Brouchet

Raymond‐Letron

et al. 2009

Circulation Research

View full text Add to dashboard Cite

Abstract-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␣ Ϫ/Ϫ ) 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 Ⅲ skin flap model Ⅲ ischemia S kin flaps are frequently used in plastic and reconstructive surgery. However, necrosis represents a major complication that may require secondary surgical interventions, generate multiple infections, and delay future treatments. Necrosis is caused by severe ischemia, resulting from impaired arterial inflow, especially in the distal part of the flap. Therapeutic angiogenesis by local administration of angiogenic growth factors fibroblast growth factor (FGF)-2 1 and vascular endothelial growth factor (VEGF), 2 and a combination of these growth factors, 3 have been successfully tested to enhance blood perfusion in affected tissues, decreasing the extent of flap necrosis. However, the safety of this approach remains controversial, 4 and no efficient therapy is currently available.Estrogens appear to be attractive candidates, because 17␤-estradiol (E2) exerts protective effects in various animal models of cardiac, brain, and hindlimb ischemia 5-7 by favoring angiogenesis, limiting endothelial dysfunction, and exerting inflammatory and antiapoptotic effects. 8,9 In elderly patients, E2 supplementation accelerates cutaneous wound healing. 10 The mechanisms underlying these changes involve an increase in transforming growth factor (TGF)-␤ 1 secretion 11 but also inhibition of the loca...

show abstract

Section: Circulation Research January 30 2009supporting

confidence: 92%

“…modulator confers estrogenic effect in various vascular systems 43,44 are in agreement with the vascular protection evidenced in the present model.…”

Section: Discussionsupporting

confidence: 76%

Prevention of Skin Flap Necrosis by Estradiol Involves Reperfusion of a Protected Vascular Network

Toutain

Brouchet

Raymond‐Letron

et al. 2009

Circulation Research

View full text Add to dashboard Cite

show abstract

“…Although experimental evidence obtained in animal models and in humans suggests that estrogen plays an important role in modifying the response of blood vessels in females to vasoactive substances (29,33,35,58,62,(65)(66)(67), the results of the present study indicate that genetic architecture is sex specific and also contributes in an important way to sexual dimorphism in phenotypic expression. In this regard, the results of the present study suggest additional avenues of investigation in evaluating sex-specific determinants of vascular reactivity.…”

Section: Discussioncontrasting

confidence: 61%

Sex-specific differences in chromosome-dependent regulation of vascular reactivity in female consomic rat strains from a SS × BN cross

Kunert¹,

Dwinell²,

Drenjančević-Perić³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

High-throughput studies in the Medical College of Wisconsin Program for Genomic Applications (Physgen) were designed to link chromosomes with physiological function in consomic strains derived from a cross between Dahl salt-sensitive SS/JrHsdMcwi (SS) and Brown Norway normotensive BN/NHsdMcwi (BN) rats. The specific goal of the vascular protocol was to characterize the responses of aortic rings from these strains to vasoconstrictor and vasodilator stimuli (phenylephrine, acetylcholine, sodium nitroprusside, and bath hypoxia) to identify chromosomes that either increase or decrease vascular reactivity to these vasoactive stimuli. Because previous studies demonstrated sex-specific quantitative trait loci (QTLs) related to regulation of cardiovascular phenotypes in an F2 cross between the parental strains, males and females of each consomic strain were included in all experiments. As there were significant sex-specific differences in aortic sensitivity to vasoconstrictor and vasodilator stimuli compared with the parental SS strain, we report the results of the females separately from the males. There were also sex-specific differences in aortic ring sensitivity to these vasoactive stimuli in consomic strains that were fed a high-salt diet (4% NaCl) for 3 wk to evaluate salt-induced changes in vascular reactivity. Differences in genetic architecture could contribute to sex-specific differences in the development and expression of cardiovascular diseases via differential regulation and expression of genes. Our findings are the first to link physiological traits with specific chromosomes in female SS rats and support the idea that sex is an important environmental variable that plays a role in the expression and regulation of genes.

show abstract

“…Such studies demonstrated that tamoxifen attenuates the vasoconstrictor response observed in estrogen deficiency (35,36). Treatment with tamoxifen also normalizes the contractile response mediated by phenylephrine in isolated cerebral arteries of OVX animals (24).…”

Section: Discussionmentioning

confidence: 96%

Effect of tamoxifen on the coronary vascular reactivity of spontaneously hypertensive female rats

Borgo

Lopes

Gouvêa

et al. 2011

Braz J Med Biol Res

View full text Add to dashboard Cite

Tamoxifen and estrogen attenuate enhanced vascular reactivity induced by estrogen deficiency in rat carotid arteries

Cited by 7 publications

References 35 publications

Prevention of Skin Flap Necrosis by Estradiol Involves Reperfusion of a Protected Vascular Network

Prevention of Skin Flap Necrosis by Estradiol Involves Reperfusion of a Protected Vascular Network

Sex-specific differences in chromosome-dependent regulation of vascular reactivity in female consomic rat strains from a SS × BN cross

Effect of tamoxifen on the coronary vascular reactivity of spontaneously hypertensive female rats

Contact Info

Product

Resources

About