Inhibition of neointima formation by local delivery of estrogen receptor alpha and beta specific agonists
Autor: | Ko Willems van Dijk, Paul H.A. Quax, J. Wouter Jukema, Margreet R. de Vries, Nuno Pires, Louis M. Havekes, Rune R. Frants, Yvonne D. Krom |
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Rok vydání: | 2006 |
Předmět: |
Neointima
Agonist Male medicine.medical_specialty Physiology medicine.drug_class Estrogen receptor Mice Phenols Physiology (medical) Internal medicine Nitriles medicine Animals Estrogen Receptor beta cardiovascular diseases Methylpiperidinopyrazole Receptor Estrogen receptor beta Cell Proliferation Drug Implants Estradiol Chemistry Reverse Transcriptase Polymerase Chain Reaction Estrogen Receptor alpha musculoskeletal system Immunohistochemistry Femoral Artery Mice Inbred C57BL Endocrinology Estrogen Models Animal cardiovascular system Pyrazoles Propionates Cardiology and Cardiovascular Medicine Tunica Intima Estrogen receptor alpha |
Zdroj: | Cardiovascular research. 73(1) |
ISSN: | 0008-6363 |
Popis: | Objective: Neointima formation is the underlying mechanism of (in-stent) restenosis. 17β-Estradiol (E2) is known to inhibit injury-induced neointima formation and post-angioplasty restenosis. Estrogen receptor alpha (ERα) has been demonstrated to mediate E2 anti-restenotic properties. However, the role of estrogen receptor beta (ERβ) is not fully elucidated. In the present study, the specific role of vascular ERα and ERβ in neointima formation is assessed. Methods and results: Neointima formation was induced by placement of a perivascular cuff around the femoral artery of male C57BL/6J mice. E2-eluting cuffs significantly inhibited cuff-induced neointima formation. To address the specific roles of ERα and ERβ on neointima formation, the ERα-selective agonist 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)tris-phenol (PPT) and the ERβ-selective agonist 2,3-bis(4-hydroxy-phenyl)-propionitrile (DPN) were applied via a drug-eluting cuff. PPT inhibited neointima formation at low but not at high concentrations. Conversely, DPN inhibited neointima formation dose dependently. To demonstrate the specificity of these responses, an ERα-selective antagonist, MPP, was also used in combination with E2, PPT, or DPN. While the effect of PPT on neointima formation inhibition was blocked by co-delivery of MPP, E2 and DPN could still inhibit neointima formation. Conclusions: Our data suggest that, in addition to ERα, specific ERβ activation inhibits neointima formation in a mouse model of restenosis. These data reveal a yet unidentified protective role of ERβ on neointima formation. © 2006 European Society of Cardiology. |
Databáze: | OpenAIRE |
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