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Selective estrogen receptor‐α agonist provides widespread heart and vascular protection with enhanced endothelial progenitor cell mobilization in the absence of uterotrophic action
Author(s) -
Bolego Chiara,
Rossoni Giuseppe,
Fadini Gian Paolo,
Vegeto Elisabetta,
Pinna Christian,
Albiero Mattia,
Boscaro Elisa,
Agostini Carlo,
Avogaro Angelo,
Gaion Rosa Maria,
Cignarella Andrea
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-139220
Subject(s) - agonist , medicine , endocrinology , estrogen receptor , estrogen , progenitor cell , endothelial progenitor cell , in vivo , receptor , pharmacology , biology , stem cell , microbiology and biotechnology , cancer , breast cancer
The beneficial effects of estrogens on the cardiovascular system are associated with adverse effects on reproductive tissues. On the basis of previous work indicating a major role for estrogen receptor (ER)‐α in maintaining cardiovascular health, we evaluated the tissue selectivity of the ERα‐selective agonist propyl pyrazole triol (PPT) compared with 17ß‐estradiol (E2) invivo. Four weeks postovariectomy, equimolar doses of PPT and E2 were administered to rats in subcutaneous implants for 5 d. Both treatments restored rapid vasorelaxation of aortic tissue to estrogenic agents and prevented coronary hyperresponsiveness to angiotensin II in isolated heart preparations. Accordingly, multiple endpoints of myocardial ischemia‐reperfusion injury exacerbated by ovariectomy returned to baseline following treatment. These protective effects were linked to increased in vivo levels of endothelial progenitor cells (EPCs). Human EPC function was enhanced in vitro after PPT treatment. In sharp contrast to E2, PPT treatment had no effect on uterine weight and histomorphology except for vessel density, and failed to up‐regulate classic estrogen target genes. Dissection of the effects on vascular reactivity and uterine morphology was also observed following increased exposure to PPT at a higher dose for longer time. These data provide the first in vivo evidence for tissue‐specific ERa activation. By conferring cardiovascular protection dissected from unwanted uterotrophic effects, ERa‐selective agonists may represent a potential safer alternative to natural hormones.—Bolego, C, Rossoni, G., Fadini, G. P., Vegeto, E., Pinna, C., Albiero, M., Boscaro, E., Agostini, C., Avogaro, A., Gaion, R M., Cignarella, A Selective estrogen receptor‐a agonist provides widespread heart and vascular protection with enhanced endothelial progenitor cell mobilization in the absence of uterotrophic action. FASEBJ. 24, 2262–2272 (2010). www.fasebj.org