Nitric oxide-mediated fibrinogen deposition prevents platelet adhesion and activation

Abstract

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.

Nitric oxide inhibits endothelial cell apoptosis by inhibiting cysteine‐dependent SOD1 monomerization

“…NO, which is predominantly synthesized by eNOS in endothelial cells, is a vasoactive substance secreted by endothelial cells [7]. NO has many beneficial effects, such as relaxing blood vessels, preventing platelet aggregation, inhibiting leukocyte adhesion, and controlling the proliferation of vascular smooth muscle cells [30][31][32][33]. NO displays pro-apoptotic or antiapoptotic effects [34] depending on its effective concentration, cell types, and microenvironment.…”

Molecular and metabolic characteristics of changes in the platelet sensitivity to antiplatelet therapy in patients with coronary artery disease before and after coronary artery bypass grafting

“…в адгезии лейкоцитов к эндотелиальным клеткам при воспалении и атеросклерозе, поэтому тоже блокируются клопидогрелом, что приводит к нарушению образования межклеточных "мостиков". Кроме того, лейкоцитарно-тромбоцитарные комплексы (образование которых не нарушено у чАСК пациентов) способны сами продуцировать АФК, а образующийся при этом оксид азота может снижать агрегационную активность тромбоцитов, тем самым предотвращает повторные тромбозы [14]. Поэтому в группе рАСК пациентов с ИБС на ДАТТ клинические исходы могут быть более благоприятными ввиду наличия клопидогрела.…”

Ex vivo evaluation of blood coagulation on endothelial glycocalyx-inspired surfaces using thromboelastography

“…[66,67] Even though NO can act to inhibit coagulation, it is not surprising that these surfaces did eventually coagulate after all NO was released. In addition, NO has been shown to mediate fibrinogen deposition which may further affect the formation of thrombin and change their susceptibility to heparin [25,30]. More studies are required to fully understand the mechanisms of why TiO 2 NT + PEM surfaces completely inhibited coagulation while TiO 2 NT + PEM + NO surfaces did not.…”

“…Nitric oxide, an endogenous signaling molecule, is well-known for its antiplatelet and anticoagulation properties [24]. Multiple NO-releasing surfaces have been shown to mitigate blood protein deposition, and inhibit platelet adhesion and activation [25][26][27][28][29][30]. This three-in-one promising surface has been previously proven to significantly inhibit platelet adhesion and activation in contact with human platelet-rich plasma [18].…”