Geraldes Pedro, Geoffroy Pascale, Cloutier Isabelle, Sirois Martin G, Tanguay Jean-François
Research Center, Montreal Heart Institute, Montréal, Qué., Canada.
J Vasc Res. 2008;45(6):503-11. doi: 10.1159/000128603. Epub 2008 May 2.
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.
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.
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.
Local delivery of 17betaE reduces restenosis, in part by decreasing the density of collagen type I in the neointima in PTCA and stented arteries.
经皮腔内冠状动脉成形术（PTCA）和支架植入与内膜增生及细胞外基质（ECM）积聚相关，可导致再狭窄。我们发现，局部递送17-β-雌二醇（17βE）可使PTCA和支架植入术后的再狭窄率分别降低47%和23%。由于雌激素在体外可降低I型和III型胶原蛋白的合成，我们推测局部递送17βE可能通过调节ECM表达来影响内膜增生的形成。
对猪冠状动脉进行PTCA或支架植入，并随机分为17βE组或安慰剂组。28天后，处死动物进行组织学检查及I型和III型胶原蛋白含量分析。
与PTCA节段相比，PTCA术后中膜内两种胶原蛋白亚型均增加了1.7至2.6倍，支架植入术后增加了15.7至16.1倍。在新生内膜中，支架植入动脉中III型与I型胶原蛋白的比例为2.7，而PTCA动脉中仅为0.3。在接受17βE治疗的动物的新生内膜中，PTCA术后I型胶原蛋白（而非III型）含量上调受到53%的限制，支架植入术后受到74%的限制。
局部递送17βE可降低再狭窄，部分原因是降低了PTCA和支架植入动脉新生内膜中I型胶原蛋白的密度。
