Local delivery of 17-beta-estradiol modulates collagen content in coronary porcine arteries after PTCA and stent implantation.
BACKGROUND
Percutaneous transluminal coronary angioplasty (PTCA) and stent implantation are associated with intimal hyperplasia and extracellular matrix (ECM) accumulation, resulting in restenosis. We showed that local delivery of 17-beta-estradiol (17betaE) reduced restenosis following PTCA and stent implantation by 47 and 23%, respectively. Because estrogens decreased type I and type III collagen synthesis in vitro, we hypothesized that local delivery of 17betaE may influence intimal hyperplasia formation by modulating ECM expression.


METHODS
Porcine coronary arteries underwent PTCA or stenting and were randomly assigned to 17betaE or placebo. After 28 days, animals were sacrificed for histology and collagen type I and III content analysis.


RESULTS
Both collagen subtypes increased in the media by 1.7 to 2.6-fold after PTCA and by 15.7 to 16.1-fold after stenting, as compared to PTCA segments. In the neointima, the ratio of collagen type III to type I was 2.7 in stented arteries and only 0.3 in PTCA arteries. In the neointima of 17betaE-treated animals, collagen type I (but not type III) content upregulation was limited by 53% after PTCA and by 74% after stenting.


CONCLUSIONS
Local delivery of 17betaE reduces restenosis, in part by decreasing the density of collagen type I in the neointima in PTCA and stented arteries.
Geraldes
Pedro
P
Research Center, Montreal Heart Institute, Montréal, Qué., Canada.
Geoffroy
Pascale
P
Cloutier
Isabelle
I
Sirois
Martin G
MG
Tanguay
Jean-François
JF
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation*; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D023903:Coronary Restenosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage*; D006801:Humans; D006965:Hyperplasia; D008297:Male; D015607:Stents; D013552:Swine
D024042:Collagen Type I; D024061:Collagen Type III; D004958:Estradiol