Coronary artery endothelial protection after local delivery of 17beta-estradiol during balloon angioplasty in a porcine model: a potential new pharmacologic approach to improve endothelial function.
OBJECTIVE
The goal of this research was to study the effect of locally delivered 17beta-estradiol (17beta-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-microg 17beta-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 17beta-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 17beta-E-treated arteries compared with the other two treatment groups. Arteries treated with 17beta-E showed significantly lower neointima formation, which correlated inversely with the extent of re-endothelialization and eNOS expression.


CONCLUSIONS
Locally delivered 17beta-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 17beta-E administration is a promising new approach to improve long-term results after PTCA.
Chandrasekar
B
B
Department of Medicine, Montreal Heart Institute and University of Montreal, Montreal, Canada.
Nattel
S
S
Tanguay
J F
JF
D000109:Acetylcholine / Q000494:pharmacology; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000379:methods; D000818:Animals; D006328:Cardiac Catheterization; D003131:Combined Modality Therapy; D017023:Coronary Angiography; D003327:Coronary Disease / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy*; D003329:Coronary Vasospasm / Q000209:etiology / Q000517:prevention & control; D003331:Coronary Vessels / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007261:Infusions, Intra-Arterial; D019001:Nitric Oxide Synthase / Q000032:analysis; D011897:Random Allocation; D012008:Recurrence; D016037:Single-Blind Method; D013552:Swine; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D004958:Estradiol; D019001:Nitric Oxide Synthase; D000109:Acetylcholine