(Circulation. 1997;95:1768-1772.)
© 1997 American Heart Association, Inc.
Articles |
Estradiol Accelerates Functional Endothelial Recovery After Arterial Injury
From St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass.
Correspondence to Douglas W. Losordo, MD, St Elizabeth's Medical Center, Division of Cardiovascular Research, 736 Cambridge St, Boston, MA 02135. E-mail dlosordo{at}opal.tufts.edu
Background The mechanisms of the established atheroprotective effects of estrogen have not been entirely clarified. Recent data suggest that agents that hasten the recovery of the endothelium after denuding injury will deter the development of neointimal lesions. Because estrogen has been shown to exert angiogenic effects in vitro and in vivo, we performed a series of experiments to evaluate whether estrogen was capable of accelerating reendothelialization.
Methods and Results Ovariectomized Sprague-Dawley rats received estrogen replacement therapy in the form of subcutaneously implanted pellets designed to release 1.5 or 5.0 mg 17ß-estradiol over 30 days. Deendothelializing balloon injury was performed 1 week after pellet implantation, and animals were euthanatized after 1 week for evaluation of reendothelialization (Evans blue staining) or 2 weeks for evaluation of reendothelialization and neointimal formation. At both time points, the use of estradiol caused a dose-dependent increase in reendothelialization, which was measured as absolute area and percentage of area that is reendothelialized. Estradiol accelerated functional endothelial recovery, manifested as an increase in nitric oxide production. Neointimal thickening was also shown to be inhibited in a dose-dependent fashion.
Conclusions Estrogen accelerates functional endothelial recovery after barotraumatic deendothelializing injury. These findings, along with the recent demonstration of estrogen receptor expression by endothelial cells, suggest that the antiatherogenic action of estrogen may be mediated in part through direct effects on endothelial cells.
Key Words: women • endothelium • angioplasty
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