Author + information
- Douglas E Drachman, MDa ()
- Campbell Rogers, MD
We very much appreciate the comments of Kipshidze et al. regarding our report on long-term reduction of experimental restenosis using a paclitaxel-releasing stent (1). Their insights underscore the challenges we all face in translating “bench-top” triumphs to techniques that benefit our patients.
It is interesting to consider the role played by the estrogen receptor in smooth muscle cell migration and proliferation (2), and it will be important to determine whether paclitaxel’s antirestenotic effects are, at least in part, effected through this receptor system. It is worth noting, however, that paclitaxel’s effects are myriad, and that attributing all to plasma membrane estrogen receptors may not be accurate. Such mechanistic insight may extend our understanding of clinical restenosis.
We reiterate concerns that experimental models of endothelial cell function are incomplete and may not always mirror responses in humans. Following experimental arterial injury, the endothelium plays an important role in guiding the healing process, modulating neointimal proliferation, controlling extracellular matrix deposition, regulating vasomotor tone, and protecting against luminal thrombus deposition. Although present laboratory methods allow us to examine the histologic impact of arterial injury on endothelial viability, specific aspects of endothelial cell function are more difficult to characterize. In particular, the scaffolding effect of an endoluminal stent renders impossible examination of the influence of endothelial function on vasomotor tone. Nevertheless, our results demonstrating von Willebrand factor (vWf) immunoreactivity indicate complete anatomic endothelialization of nondenuded arteries at three days and significant reendothelialization in denuded vessels 180 days following paclitaxel-releasing stent implantation. Smooth muscle cells on the surface would not possess vWf immunoreactivity.
In our study, the presence of collagen was markedly reduced by paclitaxel up to six months following stent implantation. The persistence of fibrin and inflammatory cells and relative absence of collagen or smooth muscle cells in the neointima indicate near-total arrest of the healing process. By examining the impact of paclitaxel on collagen deposition and other wound-healing parameters, we may gain critical insights into the determinants of clinical restensosis and potential therapeutic techniques.
- American College of Cardiology