Coronary artery endothelial protection after local delivery of 17β-estradiol during balloon angioplasty in a porcine model:: A potential new pharmacologic approach to improve endothelial function

Coronary artery endothelial protection after local delivery of 17β-estradiol during balloon angioplasty in a porcine model:: A potential new pharmacologic approach to improve endothelial function
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DOI:
10.1016/s0735-1097(01)01552-2
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发表时间:
2001-11-01
影响因子:
24
通讯作者:
Tanguay, JF
Tanguay, JF
中科院分区:
医学1区
文献类型:
--
作者:
Chandrasekar, B;Nattel, S;Tanguay, JF

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目的 本研究的目的是研究血管成形术期间局部递送 17β-雌二醇 (17β-E) 对经皮腔内冠状动脉成形术 (PTCA) 后 4 周内皮功能的影响。每条动脉被随机分配给局部递送的 600 杯 17 beta-E、等体积的载体 (V) 或单独的 PTCA。 4 周后,通过冠状动脉内乙酰胆碱 (Ach) 输注进行血管造影和免疫组织化学评估内皮功能的改善情况。 结果 在 10(-5) mol/l 和 10(-4) mol/l Ach 时,单独使用 PTCA 治疗的动脉(分别为 p < 0.01 和 p < 0.0001)和 PTCA 加 V 治疗的动脉出现显着的血管收缩。 (分别为 p < 0.02 和 p < 0.001)。在接受 PTCA 加 17 β-E 治疗的动脉中未观察到对 Ach 的显着血管收缩反应。 PTCA 后 4 周的血管免疫组织化学显示,与其他两个治疗组相比,PTCA 加 17 β-E 治疗的动脉中再内皮化 (p < 0.0005) 和内皮一氧化氮合酶 (eNOS) 表达 (p < 0.0005) 增强。用 17 β -F 治疗的动脉显示新内膜形成显着降低,这与再内皮化程度和 eNOS 表达呈反比。 结论 局部递送 17 β -E 可能通过改善 eNOS 表达,显着增强 PTCA 后的再内皮化和内皮功能。由于内皮功能障碍可促进再狭窄和冠状动脉痉挛,因此局部 17β-E 给药是改善 pTCA 后长期结果的一种有前途的新方法。 (J Am Coll Cardiol 2001;38: 1570-6) (C) 2001 年,美国心脏病学会。
OBJECTIVES The goal of this research was to study the effect of locally delivered 17 beta -estradiol (17 beta -E) during angioplasty on endothelial function after percutaneous transluminal coronary angioplasty (PTCA) at four weeks.BACKGROUND The endothelium plays a major role in the structural and functional integrity, of coronary arteries and is damaged by PTCA.METHODS juvenile swine were subjected to PTCA, after which each artery was randomly-assigned to 600-mug 17 beta -E delivered locally, an equal volume of vehicle (V) or PTCA alone. After four weeks, the improvement in endothelial function was assessed by angiography using intracoronary acetylcholine (Ach) infusion and by immunohistochemistry.RESULTS At 10(-5) mol/l and 10(-4) mol/l Ach, significant vasoconstriction was noted in arteries treated with PTCA alone (p < 0.01 and p < 0.0001, respectively) and with PTCA plus V (p < 0.02 and p < 0.001, respectively). No significant vasoconstrictive response to Ach was observed in arteries treated with PTCA plus 17 beta -E. Immunohistochemistry of vessels four weeks after PTCA revealed enhanced re-endothelialization (p < 0.0005) and endothelial nitric-oxide synthase (eNOS) expression (p < 0.0005) in PTCA plus 17 beta -E-treated arteries compared with the other two treatment groups. Arteries treated with 17 beta -F showed significantly lower neointima formation, which correlated inversely with the extent of re-endothelialization and eNOS expression.CONCLUSIONS Locally delivered 17 beta -E significantly enhances re-endothetialization and endothelial function after PTCA, possibly by improving the expression of eNOS. Since endothelial dysfunction can promote both restenosis and coronary spasm, local 17 beta -E administration is a promising new approach to improve long-term results after pTCA. (J Am Coll Cardiol 2001;38: 1570-6) (C) 2001 by the American College of Cardiology.