Silver nanoparticles enhance thrombus formation through increased platelet aggregation and procoagulant activity.
Despite the wide use of silver nanoparticles (nano Ag), its toxicity still remains poorly understood. In this report, nano Ag induced an increase in platelet aggregation and procoagulant activation which are the key contributors to thrombotic diseases. In freshly isolated human platelets, nano Ag induced platelet aggregation and procoagulant activation evident by increased phosphatidylserine exposure and thrombin generation. Interestingly, the sub-threshold level of thrombin enhanced nano Ag-induced platelet activation significantly indicating that the prothrombotic effects of nano Ag might be further potentiated in activated platelets. An increase in intracellular calcium mediated nano Ag induced platelet activation and P-selectin expression, and serotonin release was also enhanced by nano Ag. Consistent with the in vitro results, exposure to nano Ag (0.05-0.1 mg/kg i.v. or 5-10 mg/kg intratracheal instillation) in vivo enhanced venous thrombus formation, platelet aggregation, and phosphatidylserine externalization ex vivo in rats suggesting that nano Ag, indeed, does enhance thrombus formation through platelet activation.
Jun
Eun-Ah
EA
College of Pharmacy, Seoul National University, Shinrim-dong San 56-1, Gwanak-ku, Seoul, Korea.
Lim
Kyung-Min
KM
Kim
Keunyoung
K
Bae
Ok-Nam
ON
Noh
Ji-Yoon
JY
Chung
Kyu-Hyuck
KH
Chung
Jin-Ho
JH
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles / Q000009:adverse effects*; D019007:P-Selectin / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D012834:Silver / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000139:chemically induced*
D019007:P-Selectin; D010718:Phosphatidylserines; D012701:Serotonin; D012834:Silver; D013917:Thrombin; D002118:Calcium