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

OBJECTIVES The goal of this research was to study the effect of locally del ivered 17 beta -estradiol (17 beta -E) during angioplasty on endothelial fu nction after percutaneous transluminal coronary angioplasty (PTCA) at four weeks. BACKGROUND The endothelium plays a major role in the structural and functio nal 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 endothel ial 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, res pectively) and with PTCA plus V (p < 0.02 and p < 0.001, respectively). No significant vasoconstrictive response to Ach was observed in arteries treat ed with PTCA plus 17 beta -E. Immunohistochemistry of vessels four weeks af ter PTCA revealed enhanced re-endothelialization (p < 0.0005) and endotheli al nitric-oxide synthase (eNOS) expression (p < 0.0005) in PTCA plus 17 bet a -E-treated arteries compared with the other two treatment groups. Arterie s treated with 17 beta -F showed significantly lower neointima formation, w hich correlated inversely with the extent of re-endothelialization and eNOS expression. CONCLUSIONS Locally delivered 17 beta -E significantly enhances re-endothet ialization and endothelial function after PTCA, possibly by improving the e xpression of eNOS. Since endothelial dysfunction can promote both restenosi s and coronary spasm, local 17 beta -E administration is a promising new ap proach to improve long-term results after pTCA. (J Am Coll Cardiol 2001;38: 1570-6) (C) 2001 by the American College of Cardiology.