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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 upregulate surface receptors and induce platelet aggregation. Nanoparticles induce GPIIb/IIIa activation (A), SELP expression (B), and platelet aggregation (C). The use of phenanthroline (Phen) and apyrase (Apyr), but not acetylsalicylic acid (ASA), inhibits 10SiNP-induced platelet aggregation (D). A mixture of these three inhibitors also inhibited nanoparticle-induced platelet aggregation (D). Collagen (Coll) was used as a positive control for platelet aggregation. The GPIIb/IIIa activation (A) and SELP expression (B) induced by each nanoparticle treatment is expressed relative to unstimulated (resting) platelets.Notes: All values are mean ± SEM of n = 4. One-way ANOVA, Tukey-Kramer post test: *P < 0.05; **P < 0.01; ***P < 0.001 compared with resting platelets (RP) (A–C). One-way ANOVA, Tukey-Kramer post test: ^^P < 0.01; ^^^P < 0.001 compared with 10 μg/mL 10SiNP (D).Abbreviations: SEM, standard error of the mean; SiNP, silica nanoparticles.
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f3-ijn-7-631: Amorphous SiNP upregulate surface receptors and induce platelet aggregation. Nanoparticles induce GPIIb/IIIa activation (A), SELP expression (B), and platelet aggregation (C). The use of phenanthroline (Phen) and apyrase (Apyr), but not acetylsalicylic acid (ASA), inhibits 10SiNP-induced platelet aggregation (D). A mixture of these three inhibitors also inhibited nanoparticle-induced platelet aggregation (D). Collagen (Coll) was used as a positive control for platelet aggregation. The GPIIb/IIIa activation (A) and SELP expression (B) induced by each nanoparticle treatment is expressed relative to unstimulated (resting) platelets.Notes: All values are mean ± SEM of n = 4. One-way ANOVA, Tukey-Kramer post test: *P < 0.05; **P < 0.01; ***P < 0.001 compared with resting platelets (RP) (A–C). One-way ANOVA, Tukey-Kramer post test: ^^P < 0.01; ^^^P < 0.001 compared with 10 μg/mL 10SiNP (D).Abbreviations: SEM, standard error of the mean; SiNP, silica nanoparticles.

Mentions: We studied the ability of SiNP to induce platelet aggregation. Our results demonstrate that amorphous SiNP induce activation of GPIIb/IIIa as well as expression of SELP in the platelet surface membrane (Figure 3A and B). Importantly, platelet receptor activation and expression was inversely proportional to nanoparticle size and directly proportional to particle concentration. Indeed, the smallest nanoparticles (10SiNP) induced GPIIb/IIIa activation and SELP expression when used at a low concentration (10 μg/mL). In contrast, an equal concentration of larger nanoparticles (50SiNP, 150SiNP, and 500SiNP) did not influence platelet receptors. However, when used at a high concentration (100 μg/mL), 50SiNP induced both GPIIb/IIIa activation and SELP expression. Moreover, 200 μg/mL 150SiNP and 500SiNP induced SELP expression.


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 upregulate surface receptors and induce platelet aggregation. Nanoparticles induce GPIIb/IIIa activation (A), SELP expression (B), and platelet aggregation (C). The use of phenanthroline (Phen) and apyrase (Apyr), but not acetylsalicylic acid (ASA), inhibits 10SiNP-induced platelet aggregation (D). A mixture of these three inhibitors also inhibited nanoparticle-induced platelet aggregation (D). Collagen (Coll) was used as a positive control for platelet aggregation. The GPIIb/IIIa activation (A) and SELP expression (B) induced by each nanoparticle treatment is expressed relative to unstimulated (resting) platelets.Notes: All values are mean ± SEM of n = 4. One-way ANOVA, Tukey-Kramer post test: *P < 0.05; **P < 0.01; ***P < 0.001 compared with resting platelets (RP) (A–C). One-way ANOVA, Tukey-Kramer post test: ^^P < 0.01; ^^^P < 0.001 compared with 10 μg/mL 10SiNP (D).Abbreviations: SEM, standard error of the mean; SiNP, silica nanoparticles.
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getmorefigures.php?uid=PMC3278227&req=5

f3-ijn-7-631: Amorphous SiNP upregulate surface receptors and induce platelet aggregation. Nanoparticles induce GPIIb/IIIa activation (A), SELP expression (B), and platelet aggregation (C). The use of phenanthroline (Phen) and apyrase (Apyr), but not acetylsalicylic acid (ASA), inhibits 10SiNP-induced platelet aggregation (D). A mixture of these three inhibitors also inhibited nanoparticle-induced platelet aggregation (D). Collagen (Coll) was used as a positive control for platelet aggregation. The GPIIb/IIIa activation (A) and SELP expression (B) induced by each nanoparticle treatment is expressed relative to unstimulated (resting) platelets.Notes: All values are mean ± SEM of n = 4. One-way ANOVA, Tukey-Kramer post test: *P < 0.05; **P < 0.01; ***P < 0.001 compared with resting platelets (RP) (A–C). One-way ANOVA, Tukey-Kramer post test: ^^P < 0.01; ^^^P < 0.001 compared with 10 μg/mL 10SiNP (D).Abbreviations: SEM, standard error of the mean; SiNP, silica nanoparticles.
Mentions: We studied the ability of SiNP to induce platelet aggregation. Our results demonstrate that amorphous SiNP induce activation of GPIIb/IIIa as well as expression of SELP in the platelet surface membrane (Figure 3A and B). Importantly, platelet receptor activation and expression was inversely proportional to nanoparticle size and directly proportional to particle concentration. Indeed, the smallest nanoparticles (10SiNP) induced GPIIb/IIIa activation and SELP expression when used at a low concentration (10 μg/mL). In contrast, an equal concentration of larger nanoparticles (50SiNP, 150SiNP, and 500SiNP) did not influence platelet receptors. However, when used at a high concentration (100 μg/mL), 50SiNP induced both GPIIb/IIIa activation and SELP expression. Moreover, 200 μg/mL 150SiNP and 500SiNP induced SELP expression.

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