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This version published online on August 30, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-0419
A more recent version of this article appeared on November 1, 2005
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Submitted on February 28, 2005
Accepted on August 24, 2005

Small artery endothelial dysfunction in post-menopausal women: in vitro function, morphology and modification by estrogen and SERMs

Karolina Kublickiene MD, PhD*, Eimantas Svedas MD, Britt-Marie Landgren MD, PhD, Milita Crisby MD, PhD, Nasrin Nahar MD, Henry Nisell MD, PhD, and Lucilla Poston PhD

Institution for Clinical Science, Intervention and Technology (CLINTEC), Department of Obstetrics and Gynecology, Department of Neurotec, Section for Experimental Geriatrics, Karolinska Institutet, Karolinska University Hospital-Huddinge, 14186 Stockholm, Sweden and Maternal and Fetal Research Unit, Division of Reproductive Health, Endocrinology and Development, King's College London, SE1 7EH UK

* To whom correspondence should be addressed. E-mail: karolina.kublickiene{at}klinvet.ki.se.

Objective: To assess vascular endothelial function and morphology in resistance vasculature from healthy pre- and post-menopausal women in vitro, and to determine potential mechanisms of vascular protection by estrogenic compounds.

Methods: Arteries ({approx}220 µm) were dissected from sc fat biopsies obtained from healthy pre-menopausal and post-menopausal women. Flow-mediated dilatation, agonist induced endothelium-dependent and independent relaxation, and myogenic responses to changes in intraluminal pressure were evaluated before and after incubation (3 h) with 17{beta}-estradiol, propyl pyrazole triol (PPT, a selective estrogen receptor (ER) {alpha} agonist), raloxifene (a second-generation selective ER modulator) and the phytoestrogen, genistein, using pressure myography technique. In addition, endothelial morphology was assessed in arteries from pre-and post-menopausal women, and distribution of ERs within the artery wall from post-menopausal women was evaluated.

Results: Functional and morphological disturbances of endothelial function were observed in small arteries from post-menopausal women. Incubation with 17{beta}-estradiol improved post-menopausal resistance artery function: an affect mimicked by PPT but not raloxifene or genistein. Immunohistochemical staining revealed similar expression of ER{alpha} and ER{beta} in the smooth muscle of arteries from post-menopausal women; however ER{alpha} was dominant in endothelium.

Conclusions: The resistance arteries from post-menopausal women show functional and morphological abnormalities. ER{alpha} may contribute to vascular protection by estrogens in the peripheral resistance circulation in post-menopausal women. Selective ER{alpha} agonists warrant further investigation as therapeutic agents for prevention of cardiovascular disease in post-menopausal women.
Key words: menopause • small artery • estrogen • NO • SERMs • receptor




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