Nitric oxide-mediated fibrinogen deposition prevents platelet adhesion and activation.

Thrombosis is one of the most critical challenges faced by successful clinical use of blood-contacting medical devices. The formation of blood clots on medical device surfaces is a multistep process that includes protein adsorption, platelet adhesion and activation, and platelet aggregation, resulting in platelet consumption and blockage of blood flow. Without proper treatment, thrombosis will lead to ultimate device failure and create complications in patients. Nitric oxide (NO), a small signaling molecule generated from natural endothelial cells, has been widely shown to reduce platelet adhesion and activation, which occurs in the second step of blood clotting cascade. However, few studies have investigated the effect of NO on protein adsorption, which is the first step of blood clotting cascade. In this study, the effects of NO on fibrinogen (Fb) adsorption and subsequent effects of Fb on platelet adhesion and activation were investigated. This was done by using a model NO-releasing polymer film system, plasticized poly(vinyl chloride) (PVC) and -nitrosoglutathione, to examine how NO-mediated pre-adsorbed Fb, a major blood serum protein that initiates the blood clotting cascade, affects platelet adhesion and activation. The NO-releasing polymer films were found to increase Fb adsorption, but decrease platelet adhesion and activation on the surface when compared to plasticized PVC control films. Further, to eliminate the effects of NO on platelets, NO-releasing polymer films were first exposed to Fb and then incubated until all NO was released. This experiment isolates the effect of NO-mediated pre-adsorbed Fb on platelets in the absence of continuing NO release. Surprisingly, the results show that films with adsorbed Fb that no longer release NO continue to prevent platelet adhesion and activation. This study suggests that NO can affect adsorbed Fb to further prevent platelet adhesion and activation.