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

Corbalan JJ, Medina C, Jacoby A, Malinski T, Radomski MW - Int J Nanomedicine (2012)

Bottom Line: However, an increased number of studies indicate that this exposure may result in cardiovascular inflammation and damage.A high ratio of nitric oxide to peroxynitrite concentrations ([NO]/[ONOO(-)]) is crucial for cardiovascular homeostasis and platelet hemostasis.Nanoparticle-platelet interaction was examined using transmission electron microscopy.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences, Panoz Institute, Trinity College Dublin, Ireland.

ABSTRACT

Background: Amorphous silica nanoparticles (SiNP) can be used in medical technologies and other industries leading to human exposure. However, an increased number of studies indicate that this exposure may result 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 the influence of SiNP on the platelet [NO]/[ONOO(-)] balance and platelet aggregation.

Methods: Nanoparticle-platelet interaction was examined using transmission electron microscopy. Electrochemical nanosensors were used to measure the levels of NO and ONOO(-) released by platelets upon nanoparticle stimulation. Platelet aggregation was studied using light aggregometry, flow cytometry, and phase contrast microscopy.

Results: Amorphous SiNP induced NO release from platelets followed by a massive 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 the platelet surface membrane, and led to platelet aggregation via adenosine diphosphate and matrix metalloproteinase 2-dependent mechanisms. Importantly, all the effects on platelet aggregation were inversely proportional to nanoparticle size.

Conclusions: The exposure of platelets to amorphous SiNP induces a critically low [NO]/[ONOO(-)] ratio leading to platelet aggregation. These findings provide new insights into the pharmacological profile of SiNP in platelets.

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Related in: MedlinePlus

Amorphous SiNP interact with human platelets. As shown by TEM, after exposure of human platelets to 10SiNP (10 μg/mL), nanoparticles rapidly interacted with the platelet surface membrane (B) and induced aggregation (C and D). Unstimulated (resting) platelets were also presented (A).Notes: Scale bars represent 500 nm in A, C, and D; and 100 nm in B.Abbreviations: SiNP, silica nanoparticles; gr, platelet granule; TEM, transmission electron microscopy.
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f1-ijn-7-631: Amorphous SiNP interact with human platelets. As shown by TEM, after exposure of human platelets to 10SiNP (10 μg/mL), nanoparticles rapidly interacted with the platelet surface membrane (B) and induced aggregation (C and D). Unstimulated (resting) platelets were also presented (A).Notes: Scale bars represent 500 nm in A, C, and D; and 100 nm in B.Abbreviations: SiNP, silica nanoparticles; gr, platelet granule; TEM, transmission electron microscopy.

Mentions: We studied nanoparticle–platelet interactions and uptake using TEM (Figure 1). Electron micrographs showed amorphous SiNP forming agglomerates. These agglomerates were located within platelet aggregates, dispersed among platelets and interacting with the plasma membrane (Figure 1B–D). Nanoparticles also internalized and distributed into the platelet cytoplasm (Figure 1C and D). We also observed degranulated platelets indicating platelet activation (Figure 1C and D).


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

Corbalan JJ, Medina C, Jacoby A, Malinski T, Radomski MW - Int J Nanomedicine (2012)

Amorphous SiNP interact with human platelets. As shown by TEM, after exposure of human platelets to 10SiNP (10 μg/mL), nanoparticles rapidly interacted with the platelet surface membrane (B) and induced aggregation (C and D). Unstimulated (resting) platelets were also presented (A).Notes: Scale bars represent 500 nm in A, C, and D; and 100 nm in B.Abbreviations: SiNP, silica nanoparticles; gr, platelet granule; TEM, transmission electron microscopy.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3278227&req=5

f1-ijn-7-631: Amorphous SiNP interact with human platelets. As shown by TEM, after exposure of human platelets to 10SiNP (10 μg/mL), nanoparticles rapidly interacted with the platelet surface membrane (B) and induced aggregation (C and D). Unstimulated (resting) platelets were also presented (A).Notes: Scale bars represent 500 nm in A, C, and D; and 100 nm in B.Abbreviations: SiNP, silica nanoparticles; gr, platelet granule; TEM, transmission electron microscopy.
Mentions: We studied nanoparticle–platelet interactions and uptake using TEM (Figure 1). Electron micrographs showed amorphous SiNP forming agglomerates. These agglomerates were located within platelet aggregates, dispersed among platelets and interacting with the plasma membrane (Figure 1B–D). Nanoparticles also internalized and distributed into the platelet cytoplasm (Figure 1C and D). We also observed degranulated platelets indicating platelet activation (Figure 1C and D).

Bottom Line: However, an increased number of studies indicate that this exposure may result in cardiovascular inflammation and damage.A high ratio of nitric oxide to peroxynitrite concentrations ([NO]/[ONOO(-)]) is crucial for cardiovascular homeostasis and platelet hemostasis.Nanoparticle-platelet interaction was examined using transmission electron microscopy.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences, Panoz Institute, Trinity College Dublin, Ireland.

ABSTRACT

Background: Amorphous silica nanoparticles (SiNP) can be used in medical technologies and other industries leading to human exposure. However, an increased number of studies indicate that this exposure may result 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 the influence of SiNP on the platelet [NO]/[ONOO(-)] balance and platelet aggregation.

Methods: Nanoparticle-platelet interaction was examined using transmission electron microscopy. Electrochemical nanosensors were used to measure the levels of NO and ONOO(-) released by platelets upon nanoparticle stimulation. Platelet aggregation was studied using light aggregometry, flow cytometry, and phase contrast microscopy.

Results: Amorphous SiNP induced NO release from platelets followed by a massive 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 the platelet surface membrane, and led to platelet aggregation via adenosine diphosphate and matrix metalloproteinase 2-dependent mechanisms. Importantly, all the effects on platelet aggregation were inversely proportional to nanoparticle size.

Conclusions: The exposure of platelets to amorphous SiNP induces a critically low [NO]/[ONOO(-)] ratio leading to platelet aggregation. These findings provide new insights into the pharmacological profile of SiNP in platelets.

Show MeSH
Related in: MedlinePlus