Nitrated Oleic Acid Coating of Nitinol Grafts to Diminish Stent-Angioplasty-Associated Thrombotic Complications

Objectives: According to the German Federal Statistical Office, the incidence of cardiovascular diseases has continued to increase and at 38.5% still represents the most frequent cause of death in Germany. Above all, arterial vascular diseases that are mainly a result of atherosclerotic changes in the vessel wall play a decisive role. Although stent angioplasty, the most common treatment for atherosclerotic vessels, is a minimally invasive procedure, the implanted foreign material can lead to inflammation processes and to restenosis or thrombosis. Therefore, our study focuses on the development of a new and efficient stent coating based on nitrated oleic acid (NO₂-OA), which modulates various antiinflammatory and antiproliferative processes via different signal pathways under physiological conditions.

Methods and Results: First, the effect on cell- and hemocompatibility of different concentrations of NO₂-OA were examined after direct contact with cells. Our data show that NO₂-OA treatment of Human Embryonic Kidney 293 (HEK293) cells and primary Human Umbilical Vein Endothelial cells (HUVECs) results in slightly improved viability, migration and proliferation of the cells. A reduction in the expression of different inflammatory genes could not be observed. Moreover, blood coagulation and various other blood parameters were not altered by the tested NO₂-OA concentrations. We further developed a covalent NO₂-OA coating for nitinol stents to ensure a stable binding of the agent on the surface. Using a dynamic in vitro thrombogenicity model, we show that the NO₂-OA-coated stents could significantly inhibit the activation of blood coagulation.

Conclusions: Overall, our NO₂-OA stent coating represents an innovative and promising concept for the improvement of stent-angioplasty-associated thrombotic complications. Hereby patients, in whom stent implantation is unavoidable, may be protected subsequently and safely from thrombotic complications and presumably restenosis.