title: Silver nanoparticles enhance thrombus formation through increased platelet aggregation and procoagulant activity.
abstract: 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.
authors.affiliation: College of Pharmacy, Seoul National University, Shinrim-dong San 56-1, Gwanak-ku, Seoul, Korea.
authors.forename: Eun-Ah
authors.initials: EA
authors.lastname: Jun
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lim
authors.forename: Keunyoung
authors.initials: K
authors.lastname: Kim
authors.forename: Ok-Nam
authors.initials: ON
authors.lastname: Bae
authors.forename: Ji-Yoon
authors.initials: JY
authors.lastname: Noh
authors.forename: Kyu-Hyuck
authors.initials: KH
authors.lastname: Chung
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Chung
mesh_terms: 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*
chemical_list: D019007:P-Selectin; D010718:Phosphatidylserines; D012701:Serotonin; D012834:Silver; D013917:Thrombin; D002118:Calcium