title: Local delivery of 17-beta-estradiol modulates collagen content in coronary porcine arteries after PTCA and stent implantation.
abstract: 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.
authors.affiliation: Research Center, Montreal Heart Institute, Montréal, Qué., Canada.
authors.forename: Pedro
authors.initials: P
authors.lastname: Geraldes
authors.forename: Pascale
authors.initials: P
authors.lastname: Geoffroy
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cloutier
authors.forename: Martin G
authors.initials: MG
authors.lastname: Sirois
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Tanguay
mesh_terms: 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
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D004958:Estradiol