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
Biology
Biomedical Research
Animal model
Estrogens
Hormones
Receptors
Restenosis
2,3 bis(4 hydroxyphenyl)propionitrile
4,4',4'' (4 propyl [1h] pyrazole 1,3,5 triyl)tris phenol
antiestrogen
estradiol
estrogen receptor alpha
estrogen receptor beta
methylpiperidinopyrazole
phenol derivative
propionitrile
pyrazole derivative
agonist
animal cell
animal model
article
controlled study
cuff
dose response
drug eluting stent
femoral artery
hormone inhibition
intima
male
mouse
nonhuman
priority journal
restenosis
sensitivity and specificity
Animals
Cell Proliferation
Drug Implants
Estradiol
Estrogen Receptor alpha
Estrogen Receptor beta
Femoral Artery
Immunohistochemistry
Male
Mice
Mice, Inbred C57BL
Models, Animal
Nitriles
Propionates
Pyrazoles
Reverse Transcriptase Polymerase Chain Reaction
Tunica 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