NEOINTIMAL TISSUE-RESPONSE AT SITES OF CORONARY STENTING IN HUMANS - MACROSCOPIC, HISTOLOGICAL, AND IMMUNOHISTOCHEMICAL ANALYSES

Background-Experimental animal studies have shown that coronary stenti ng induces neointimal proliferation. However, the histopathological ev ents after coronary stenting in humans have not been studied systemati cally. Methods and Results-We investigated 11 stented coronary arterie s (9 Palmaz-Schatz stents, 1 Wiktor stent, and 1 ACS Multi-Link stent) obtained from 11 patients who had died 2 days to 21 months after sten ting. We focused on gross, histological, and immunohistochemical aspec ts of the repair processes. Two patients developed symptoms of resteno sis. Serial sections were stained with antibodies against smooth muscl e cells (SMCs), macrophages, and endothelial cells. At 9 and 12 days a fter stenting, the stent sites showed thrombus formation with early fo rmation of neointima composed of abundant macrophages and cu-actin-neg ative spindle cells. From 64 days on, all sites with stenting showed a distinct layer of neointima, albeit to varying degrees. In nonresteno tic lesions, neointimal thickening was markedly less than in restenoti c lesions but without qualitative differences; the neointima contained macrophages but was composed predominantly of alpha-actin-positive SM Cs. Conclusions-These observations strongly support the concept that n eointimal proliferation in humans Is a process of staged redifferentia tion of SMCs, which may cause in-stent stenosis. Moreover, the exubera nt neointimal proliferation with accumulation of macrophages and exten sive neovascularization at sites of stent restenosis suggests a role f or organization of mural thrombus.