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

OBJECTIVES The goal of this research was to study the effect of locally delivered 17β-estradiol (17β-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-μg 17β-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 17β-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 17β-E-treated arteries compared with the other two treatment groups. Arteries treated with 17β-E showed significantly lower neointima formation, which correlated inversely with the extent of re-endothelialization and eNOS expression. CONCLUSIONS Locally delivered 17β-E significantly enhances re-endothelialization and endothelial function after PTCA, possibly by improving the expression of eNOS. Since endothelial dysfunction can promote both restenosis and coronary spasm, local 17β-E administration is a promising new approach to improve long-term results after PTCA.