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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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Amorphous SiNP induce platelet aggregation. Platelets were exposed to 10 μg/mL 10-nm SiNP in the absence (C) or present of inhibitors of platelet aggregation (D–G). Unstimulated (resting) platelets (A) and platelet aggregation induced by collagen (B) are also shown. Previous to the exposure to 10SiNP, platelets were incubated with acetylsalicylic acid (D), phenanthroline (E), apyrase (F) and a mixture of these three inhibitors (G).Note: Scale bars represent 100 μm.Abbreviation: SiNP, silica nanoparticles.
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f4-ijn-7-631: Amorphous SiNP induce platelet aggregation. Platelets were exposed to 10 μg/mL 10-nm SiNP in the absence (C) or present of inhibitors of platelet aggregation (D–G). Unstimulated (resting) platelets (A) and platelet aggregation induced by collagen (B) are also shown. Previous to the exposure to 10SiNP, platelets were incubated with acetylsalicylic acid (D), phenanthroline (E), apyrase (F) and a mixture of these three inhibitors (G).Note: Scale bars represent 100 μm.Abbreviation: SiNP, silica nanoparticles.

Mentions: Knowing that 10SiNP at 10 μg/mL were able to induce platelet aggregation, further experiments with selective inhibitors of the pathways leading to platelet aggregation mediated by TXA2 (ASA), ADP (apyrase), and MMP2 (phenanthroline) were carried out to characterize the mechanism of SiNP-induced platelet aggregation (Figure 3D). Our results show that incubation of platelets with both phenanthroline and apyrase, but not ASA, prior to their exposure to nanoparticles, inhibited nanoparticle-induced platelet aggregation (Figures 3D and 4).


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 induce platelet aggregation. Platelets were exposed to 10 μg/mL 10-nm SiNP in the absence (C) or present of inhibitors of platelet aggregation (D–G). Unstimulated (resting) platelets (A) and platelet aggregation induced by collagen (B) are also shown. Previous to the exposure to 10SiNP, platelets were incubated with acetylsalicylic acid (D), phenanthroline (E), apyrase (F) and a mixture of these three inhibitors (G).Note: Scale bars represent 100 μm.Abbreviation: SiNP, silica nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

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

f4-ijn-7-631: Amorphous SiNP induce platelet aggregation. Platelets were exposed to 10 μg/mL 10-nm SiNP in the absence (C) or present of inhibitors of platelet aggregation (D–G). Unstimulated (resting) platelets (A) and platelet aggregation induced by collagen (B) are also shown. Previous to the exposure to 10SiNP, platelets were incubated with acetylsalicylic acid (D), phenanthroline (E), apyrase (F) and a mixture of these three inhibitors (G).Note: Scale bars represent 100 μm.Abbreviation: SiNP, silica nanoparticles.
Mentions: Knowing that 10SiNP at 10 μg/mL were able to induce platelet aggregation, further experiments with selective inhibitors of the pathways leading to platelet aggregation mediated by TXA2 (ASA), ADP (apyrase), and MMP2 (phenanthroline) were carried out to characterize the mechanism of SiNP-induced platelet aggregation (Figure 3D). Our results show that incubation of platelets with both phenanthroline and apyrase, but not ASA, prior to their exposure to nanoparticles, inhibited nanoparticle-induced platelet aggregation (Figures 3D and 4).

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