Thrombospondin 1 as possible key factor in the hemocompatibility of endocoronary prostheses.

Intracoronary stenting has markedly improved the patency of native coronary arteries after percutaneous transluminal coronary angioplasty (PTCA). Advances in stent technology and design, including drug releasing stents, have contributed to reduce the long-term restenosis rate. However, stenosis caused by neointimal hyperplasia, vascular remodeling and thrombosis is still a major problem after endocoronary stent procedures. This study focuses on differential gene expression of circulating peripheral blood cells after 90 min exposure to stents to search for initially activated cellular pathways, which may foster restenosis. Fresh human whole blood (1 IU heparin/ml), taken from non-medicated healthy volunteers, was incubated under flow conditions in an in vitro closed-loop stent-testing model (modified Chandler-Loop). Differential gene expression compared to resting conditions and to the experimental controls was investigated by a DNA-microarray technique encoding for over 17,000 genes simultaneously. As expected, a large variety of genes showed differential gene expression. Interestingly, Thrombospondin 1 (TSP-1), which plays a key role in initial immune defense, was found to be the most markedly up-regulated gene. We propose TSP-1 expression as an early indicator for the activation of immune responses following intracoronary stenting. After clarifying the participation of TSP-1 in vivo, future studies will therefore focus on TSP-1 as a potential prognostic factor, which may also help to develop and control new surface materials with an improved biocompatibility.