In vitro evaluation of the vascular reestenosis prevention and reendotheliazation with new nitric oxide eluinting materials

Abstract

The in-stent reestenosis is observed in 20-25% of percutaneous transmural coronary angioplasty (PTCA) following bare metal stent implantation. Smooth muscle cells (SMC) differentiation and proliferation, deposition of extra - cellular matrix and adjacent endothelial prejudice are the triggers for its formation. Neointima can be prevented by drug-elution stents, such as nitric oxide (NO) donors, which promote the inhibition of vascular reestenosis and increase reendotheliazation. However, the therapeutic use of NO is limited due to its low half-life and chemical reactivity. One of the main goals of our interdisciplinary research group is developing and evaluating the NO release systems. The purpose of the present study is to establish "in vitro" protocols for the NO donor- coating stents evaluation of the cytotoxic effects, higher anti-proliferative efficacy on SMC and the viability on endothelial cells for the viabilization of pre-clinic assays. The proliferation, migration and cellular death responses will be determined on cells exposed to bare metal stent samples (1mm) and test agents. The expression of the intracellular signaling pathways related to those processes will be determined and proposed to be used as biomarkers. From these evaluations we would be able to rapidly screen and suggest the action mechanisms related to responses promoted by NO-donors coating stents. These methodologies will be suitable to establish safety margins and evaluate the anti-proliferative effects of NO-eluting biomaterials for the new formulation for cardiovascular devices. (AU)