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无定形二氧化硅纳米颗粒聚集人血小板：对血管稳态的潜在影响。

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

机构信息

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

出版信息

Int J Nanomedicine. 2012;7:631-9. doi: 10.2147/IJN.S28293. Epub 2012 Feb 7.

DOI:10.2147/IJN.S28293
PMID:22334785
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3278227/
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.

摘要

背景

无定形二氧化硅纳米颗粒（SiNP）可用于医疗技术和其他行业，导致人体暴露。然而，越来越多的研究表明，这种暴露可能导致心血管炎症和损伤。一氧化氮与过氧亚硝酸盐浓度的高比值（[NO]/[ONOO(-)])对于心血管稳态和血小板止血至关重要。因此，我们研究了 SiNP 对血小板 [NO]/[ONOO(-)]平衡和血小板聚集的影响。

方法

使用透射电子显微镜检查纳米颗粒-血小板相互作用。使用电化学纳米传感器测量血小板在纳米颗粒刺激下释放的 NO 和 ONOO(-)水平。使用光聚合仪、流式细胞术和相差显微镜研究血小板聚集。

结果

无定形 SiNP 诱导血小板释放 NO，随后大量刺激 ONOO(-)，导致[NO]/[ONOO(-)]比值不利降低。此外，SiNP 诱导血小板表面膜上选择素 P 的表达和糖蛋白 IIb/IIIa 的激活，并通过二磷酸腺苷和基质金属蛋白酶 2 依赖性机制导致血小板聚集。重要的是，所有对血小板聚集的影响都与纳米颗粒尺寸成反比。

结论

血小板暴露于无定形 SiNP 会导致[NO]/[ONOO(-)]比值严重降低，从而导致血小板聚集。这些发现为 SiNP 在血小板中的药理学特征提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f50/3278227/99d6b56caf54/ijn-7-631f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f50/3278227/fa9668064a3e/ijn-7-631f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f50/3278227/e31142c9f786/ijn-7-631f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f50/3278227/e6d2d93fa170/ijn-7-631f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f50/3278227/99d6b56caf54/ijn-7-631f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f50/3278227/fa9668064a3e/ijn-7-631f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f50/3278227/e31142c9f786/ijn-7-631f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f50/3278227/e6d2d93fa170/ijn-7-631f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f50/3278227/99d6b56caf54/ijn-7-631f4.jpg

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