Selective Estrogen Receptor Modulator Idoxifene Inhibits Smooth Muscle Cell Proliferation, Enhances Reendothelialization, and Inhibits Neointimal Formation In Vivo After Vascular Injury
| Autor: | Xin L. Ma, Padma K. Narayanan, Eliot H. Ohlstein, Tian-Li Yue, Lynne M. Vickery-Clark, Kent A. Gossett, Robert N. Willette, Barbara L. Storer, Calvert Louden, Xiang Li, Jun Chen, Juan-Li Gu |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Idoxifene medicine.medical_specialty Pathology Vascular smooth muscle Endothelium medicine.drug_class Ovariectomy Estrogen receptor Cell Count Wounds Nonpenetrating Muscle Smooth Vascular Rats Sprague-Dawley Estrogen Receptor Modulators Proliferating Cell Nuclear Antigen Physiology (medical) Internal medicine von Willebrand Factor medicine Animals Humans Carotid Stenosis Cells Cultured Cell growth business.industry Cell Cycle Immunohistochemistry Rats Disease Models Animal Tamoxifen Carotid Arteries medicine.anatomical_structure Endocrinology Estrogen Selective estrogen receptor modulator Ovariectomized rat Female Endothelium Vascular Tunica Intima Cardiology and Cardiovascular Medicine business Cell Division |
| Zdroj: | Circulation. 102:III-281 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.102.suppl_3.iii-281 |
| Popis: | Background—Idoxifene (ID) is a tissue-selective estrogen receptor modulator (SERM). The pharmacological profile of ID in animal studies suggests that it behaves like an estrogen receptor (ER) agonist in bone and lipid metabolism while having negligible ER activity on the reproductive system. It is unknown whether ID retains the vascular protective effects of estrogen.Methods and Results—In cultured vascular smooth muscle cells (VSMCs), ID inhibited platelet-derived growth factor–induced DNA synthesis and mitogenesis with IC50values of 20.4 and 27.5 nmol/L, respectively. Treatment with ID resulted in S-phase cell cycle arrest in serum-stimulated VSMCs. ID 1 to 100 nmol/L significantly protected endothelial cells from tumor necrosis factor-α (TNF-α)–induced apoptosis in vitro. Virgin Sprague-Dawley rats ovariectomized 1 week before the study were treated with ID (1 mg · kg−1· d−1) or vehicle by gavage for 3 days before balloon denudation in carotid artery. The SMC proliferation in injured vessels was determined by immunostaining for proliferating cell nuclear antigen (PCNA). The number of PCNA-positive SMCs was reduced by 69%, 82%, and 86% in the media at days 1, 3 and 7, respectively, and by 78% in the neointima at day 7 after injury in ID- versus vehicle-treated group (PPPPPConclusions—The results indicate that ID beneficially modulates the balloon denudation–induced vascular injury response. Inhibition of VSMC proliferation and acceleration of endothelial recovery likely mediate this protective effect of ID. |
| Databáze: | OpenAIRE |
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