Print Email Facebook Twitter Inhibition of neointima formation by local delivery of estrogen receptor alpha and beta specific agonists Title Inhibition of neointima formation by local delivery of estrogen receptor alpha and beta specific agonists Author Krom, Y.D. Pires, N.M.M. Jukema, J.W. de Vries, M.R. Frants, R.R. Havekes, L.M. van Dijk, K.W. Quax, P.H.A. TNO Kwaliteit van Leven Publication year 2007 Abstract 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. Subject BiologyBiomedical ResearchAnimal modelEstrogensHormonesReceptorsRestenosis2,3 bis(4 hydroxyphenyl)propionitrile4,4',4'' (4 propyl [1h] pyrazole 1,3,5 triyl)tris phenolantiestrogenestradiolestrogen receptor alphaestrogen receptor betamethylpiperidinopyrazolephenol derivativepropionitrilepyrazole derivativeagonistanimal cellanimal modelarticlecontrolled studycuffdose responsedrug eluting stentfemoral arteryhormone inhibitionintimamalemousenonhumanpriority journalrestenosissensitivity and specificityAnimalsCell ProliferationDrug ImplantsEstradiolEstrogen Receptor alphaEstrogen Receptor betaFemoral ArteryImmunohistochemistryMaleMiceMice, Inbred C57BLModels, AnimalNitrilesPropionatesPyrazolesReverse Transcriptase Polymerase Chain ReactionTunica Intima To reference this document use: http://resolver.tudelft.nl/uuid:a8c55a26-591a-46cf-8aee-29d878d89610 DOI https://doi.org/10.1016/j.cardiores.2006.10.024 TNO identifier 239820 ISSN 0008-6363 Source Cardiovascular Research, 73 (1), 217-226 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.