Angiogenesis, vascular endothelial growth factor and platelet-derived growth factor-BB expression, iron deposition, and oxidation-specific epitopes in stented human coronary arteries

Pathogenesis of in-scent restenosis remains poorly understood because infor mation from human histopathologic studies is scarce. We used an improved sa w-grinding and cutting method on methacrylate-embedded samples containing m etal stents, which allows in situ hybridization and immunohistochemical ana lysis of in-scent restenosis. Twenty-one samples were collected 3 hours to 3 years after stenting from 6 patients aged 36 to 81 years. Except in very early samples collected within hours after the stem deployment, neovascular ization was present in all segments studied. At advanced stages, extensive neovascularization was located mainly at the luminal side of the stent stru ts and was only rarely accompanied by inflammatory cells. The neovessels co localized with vascular endothelial growth factor (VEGF)-A mRNA and protein expression as well as with iron deposits and oxidation-specific epitopes, which imply the presence of chronic oxidative stress. VEGF-A expression was detected in the same areas containing macrophages, endothelial cells, and, to a lesser extent, smooth muscle cells, which also showed platelet-derive d growth factor-BB expression. We conclude that in-stem restenosis features neovascularization, VEGF-A and platelet-derived growth factor-BB expressio n, and iron deposition, which is most probably derived from microhemorrhage s. These mechanisms may play an important role in the development of neoint imal thickening and could provide useful targets for the prevention and tre atment of in-stem restenosis.