Friday, February 17, 2012

Amorphous silica nanoparticles aggregate human platelets: potential implications for vascular homeostasis.

Int J Nanomedicine. 2012; 7: 631-9
Corbalan JJ, Medina C, Jacoby A, Malinski T, Radomski MW

Amorphous silica nanoparticles (SiNP) can be used in medical technologies and other industries leading to human exposure. However, an increased series of studies indicate that this bearing may outcome in cardiovascular inflammation and damage. A high ratio of nitric oxide to peroxynitrite concentrations ([NO]/[ONOO(-)]) is crucial for cardiovascular homeostasis and platelet hemostasis. Therefore, we studied a influence of SiNP on a platelet [NO]/[ONOO(-)] balance and platelet aggregation.Nanoparticle-platelet interaction was examined using transmission nucleus microscopy. Electrochemical nanosensors were used to measure a levels of NO and ONOO(-) released by platelets upon nanoparticle stimulation. Platelet assembly was studied using light aggregometry, flow cytometry, and phase contrast microscopy.Amorphous SiNP induced NO release from platelets followed by a large stimulation of ONOO(-) leading to an unfavorably low [NO]/[ONOO(-)] ratio. In addition, SiNP induced an upregulation of selectin P expression and glycoprotein IIb/IIIa activation on a platelet surface membrane, and led to platelet assembly around adenosine diphosphate and matrix metalloproteinase 2-dependent mechanisms. Importantly, all a goods on platelet assembly were inversely proportional to nanoparticle size.The bearing of platelets to distorted SiNP induces a critically low [NO]/[ONOO(-)] ratio leading to platelet aggregation. These findings yield new insights into a pharmacological profile of SiNP in platelets.


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