BACKGROUND: In-stent restenosis (ISR) is a shortcoming of percutaneous coronary revascularization. Although neointimal cell proliferation is suspected to be the cause of this problem, little histological characterization of this tissue or data on cell replication exist. The purpose of this study was to examine the histologic features and proliferation profile of coronary ISR tissue derived from atherectomy procedures performed on patients with clinical evidence of ISR. METHODS: ISR tissue retrieved by means of atherectomy from 20 coronary lesions was subjected to histomorphological analyses and immunocytochemistry as a means of examining proteoglycan expression. Cell proliferation was assessed with 2 sensitive markers of replication, in situ hybridization for histone 3 messenger RNA expression and immunocytochemistry for Ki-67 expression. RESULTS: The ISR atherectomy specimens consisted primarily of smooth muscle cells, with occasional focal collections of inflammatory cells and organizing thrombus. All specimens had low levels of interstitial collagen and an abundant proteoglycan matrix, with biglycan being overexpressed more commonly than decorin. Cell proliferation was found in only 1 of 20 specimens (2 cells). CONCLUSION: Established ISR lesions contained an abundant proteoglycan matrix and a paucity of proliferating cells. Future therapeutic strategies for ISR should include targeting extracellular matrix production.
BACKGROUND: In-stent restenosis (ISR) is a shortcoming of percutaneous coronary revascularization. Although neointimal cell proliferation is suspected to be the cause of this problem, little histological characterization of this tissue or data on cell replication exist. The purpose of this study was to examine the histologic features and proliferation profile of coronary ISR tissue derived from atherectomy procedures performed on patients with clinical evidence of ISR. METHODS: ISR tissue retrieved by means of atherectomy from 20 coronary lesions was subjected to histomorphological analyses and immunocytochemistry as a means of examining proteoglycan expression. Cell proliferation was assessed with 2 sensitive markers of replication, in situ hybridization for histone 3 messenger RNA expression and immunocytochemistry for Ki-67 expression. RESULTS: The ISR atherectomy specimens consisted primarily of smooth muscle cells, with occasional focal collections of inflammatory cells and organizing thrombus. All specimens had low levels of interstitial collagen and an abundant proteoglycan matrix, with biglycan being overexpressed more commonly than decorin. Cell proliferation was found in only 1 of 20 specimens (2 cells). CONCLUSION: Established ISR lesions contained an abundant proteoglycan matrix and a paucity of proliferating cells. Future therapeutic strategies for ISR should include targeting extracellular matrix production.