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EXPERIMENTAL STUDY

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

Baskaran Chandrasekar, MD^*, Stanley Nattel, MD, FACC^* and Jean-François Tanguay, MD, FACC^*,*

^* Department of Medicine, Montreal Heart Institute and University of Montreal, Montreal, Canada
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada

Manuscript received October 18, 2000; revised manuscript received July 10, 2001, accepted July 23, 2001.

^* Reprint requests and correspondence: Dr. Jean-François Tanguay, Research Center, Montreal Heart Institute, 5000 Bélanger Street East, Montreal, Quebec, Canada, H1T 1C8
tanguay{at}icm.umontreal.ca

OBJECTIVES

The goal of this research was to study the effect of locally delivered 17ß-estradiol (17ß-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 17ß-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 17ß-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 17ß-E-treated arteries compared with the other two treatment groups. Arteries treated with 17ß-E showed significantly lower neointima formation, which correlated inversely with the extent of re-endothelialization and eNOS expression.

CONCLUSIONS

Locally delivered 17ß-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 17ß-E administration is a promising new approach to improve long-term results after PTCA.

Abbreviations and Acronyms   Ach = acetylcholine   eNOS = endothelial nitric oxide synthase   LAD = left anterior descending artery   PTCA = percutaneous transluminal coronary angioplasty   QCA = quantitative coronary angiography   RCA = right coronary artery   SMC = smooth muscle cell   TNF- = tumor necrosis factor-   V = vehicle   17ß-E = 17ß-estradiol

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