Expression of endothelin-converting enzyme, endothelin-1 and endothelin receptors at the site of percutaneous coronary intervention in humans

Objective The repair process at the site of injury after percutaneous coronary intervention (PCI) is dominated by neointimal formation composed mainly of smooth muscle cells (SMC). Endothelin-1 (ET-1) is a powerful vasoconstrictor and SMC mitogen. Endothelin-converting enzyme (ECE) is the final key enzyme of endothelin processing. The effects of ET-1 are mediated by binding to endothelin type A (ET A ) and endothelin type B (ET B ) receptors. The ligand/receptor/ligand-producing system (ET system) could be involved in the pathogenesis of neointimal formation in humans. Methods Fifteen post-PCI sites obtained at autopsy and eight atherectomy specimens obtained from restenotic sites were investigated using immunohistochemical single and double staining techniques. Frozen sections were stained with antibodies against ECE, ET-1, ET A and ET B receptors, SMC, macrophages and endothelial cells. Results At the early stage, less than 3 months after PCI, neointimal SMC were positive for ECE, ET-1, ET A and ET B receptors. The expression of ECE, ET-1, ET A and ET B receptors in these neointimal SMC decreased markedly from 6 months onwards. The ECE, ET-1, ET A and ET B receptor-positive cell areas were significantly (P< 0.005) greater in the first 3 months after PCI compared with 6 months or more after PCI. Atherectomy specimens also showed similar positivity. Conclusions These observations strongly suggest that the expression of ECE, ET-1, ET A and ET B receptors is enhanced in neointimal SMC at early stages after PCI injury in human coronary arteries. The increased expression of the ET system may contribute to SMC proliferation/migration and vasoconstriction in human post-PCI coronary lesions.