Serial extracellular matrix changes in neointimal lesions of human coronary artery after percutaneous transluminal coronary angioplasty: clinical significance of early tenascin-C expression

It has become clear that deposition of extracellular matrix(ECM) proteins i s a major cause of human restenosis after percutaneous coronary angioplasty (PTCA). To define the composition and organization of the involved ECM in human restenotic tissue, we morphologically and semiquantitatively analyzed specimens obtained by means of directional coronary atherectomy at various stages after PTCA with anti-fibronectin, tenascin-C, collagens I and III, and PG-M/versican antibodies. Tenascin-C deposition transiently increased w ithin 1 month after PTCA, when smooth muscle cell migration and proliferati on was active. Following the disappearance of tenascin-C, PG-M/versican acc umulation increased and peaked between 1 month and 3 months when clinical r estenosis was most actively progressing. At later stages, the PG-M/versican was replaced by a more mature ECM consisting of collagens I and III. The v olume ratio of elastin remained at a low level throughout. Our results demo nstrate that the matrix proteins of human restenotic lesions sequentially c hange after angioplasty and that tenascin-C could be a key molecule in the early stages.