Estrogen-eluting stent implantation inhibits neointimal formation and extracellular signal-regulated kinase activation.
OBJECTIVE
The goal of this study was to evaluate the efficacy and the mechanism of 17beta-estradiol-eluting stents on inhibiting neointimal formation of abdominal aortas in rabbits fed with high fat diet.


BACKGROUND
Animal experiments have shown that local delivery of estrogen reduced neointimal formation after coronary angioplasty. Preliminary trial of estrogen-eluting stent implantation in patients with coronary disease also suggests a reduction in restenosis.


METHODS
We implanted 17beta-estradiol-eluting stents, or control phosphorylcholine- coated stents, or bare metal stents of abdominal aortas in rabbits fed with high fat diet. Histology, immunohistochemistry, and Western blot analysis were used to assess the efficacy and mechanism of inhibiting neointimal formation of 17beta-estradiol-eluting stents.


RESULTS
Western blot analysis revealed marked increase in ERK phosphorylation in 30 min after deployment of phosphorylcholine-coated or bare metal stents, indicating activation of MAP kinase pathway. Immunohistochemistry showed intense staining of phospho-ERK in the medial smooth muscle cells in stent-implanted region. Extensive neointimal hyperplasia developed 12 weeks after stenting. In contrast, we observed significant inhibition of ERK phosphorylation and neointimal thickening in estrogen-eluting stent-implanted animals. Immunohistochemistry of factor VIII-related antigen demonstrated an accelerated reendothelialization as compared with the bare metal stent or phosphorylcholine-coated stent-implanted controls.


CONCLUSIONS
Current study suggests that estrogen-eluting stents reduce neointimal formation and hence prevent restenosis after angioplasty possibly by inhibiting ERK activation in smooth muscle cells and promoting reendothelialization.
Han
Yaling
Y
Department of Cardiology, Cardiovascular Research Institute, Shenyang Northern Hospital, Shenyang, China. hanyaling@263.net
Liang
Ming
M
Kang
Jian
J
Qi
Yanmei
Y
Deng
Jie
J
Xu
Kai
K
Yan
Chenghui
C
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D020099:Coated Materials, Biocompatible; D023903:Coronary Restenosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage* / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D010767:Phosphorylcholine; D011817:Rabbits; D015607:Stents
D020099:Coated Materials, Biocompatible; D010767:Phosphorylcholine; D004958:Estradiol; D048049:Extracellular Signal-Regulated MAP Kinases