Titanium dioxide nanoparticles enhance thrombosis through triggering the phosphatidylserine exposure and procoagulant activation of red blood cells.
Titanium dioxide nanoparticles enhance thrombosis through triggering the phosphatidylserine exposure and procoagulant activation of red blood cells.
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DOI：
10.1186/s12989-021-00422-1
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发表时间：
2021-08-04
影响因子：
10
通讯作者：
Pi J
中科院分区：
文献类型：
--
作者：
Bian Y;Chung HY;Bae ON;Lim KM;Chung JH;Pi J
随着纳米二氧化钛（TiO 2）在生物医学领域应用的不断扩大，其潜在的健康危害引起了公众的关注。在这里，我们证明了TiO 2纳米颗粒可以增加磷脂酰丝氨酸（PS）暴露和红细胞（RBC）的促凝活性，这可能有助于血栓形成。我们使用从健康男性志愿者新鲜分离的RBC进行体外研究。TiO 2 NPs暴露（1025 μg/mL）诱导PS暴露和微泡（MV）生成，并伴有RBC形态学变化。虽然在暴露于TiO 2 NPs后没有观察到ROS产生，但细胞内钙增加，caspase-3被激活，这上调了scramblase活性，导致PS暴露。暴露于TiO 2 NPs的RBC可以增加促凝血活性，如通过加速凝血酶生成以及RBC-内皮细胞粘附和RBC-RBC聚集的增强所测量的。证实了体外RBC的促凝血活化，大鼠暴露于TiO 2 NPs（2 mg/kg静脉注射）增加了静脉血栓形成模型中的血栓形成。总的来说，这些结果表明，TiO 2纳米颗粒可能通过促进红细胞的促凝活性而具有促血栓形成的风险，这需要注意其生物医学应用。在线版本包含补充材料，可通过10.1186/s12989-021-00422-1获得。
Expanding biomedical application of anatase titanium dioxide (TiO2) nanoparticles (NPs) is raising the public concern on its potential health hazards. Here, we demonstrated that TiO2 NPs can increase phosphatidylserine (PS) exposure and procoagulant activity of red blood cells (RBCs), which may contribute to thrombosis. We conducted in vitro studies using RBCs freshly isolated from healthy male volunteers. TiO2 NPs exposure (≦ 25 μg/mL) induced PS exposure and microvesicles (MV) generation accompanied by morphological changes of RBCs. While ROS generation was not observed following the exposure to TiO2 NPs, intracellular calcium increased and caspase-3 was activated, which up-regulated scramblase activity, leading to PS exposure. RBCs exposed to TiO2 NPs could increase procoagulant activity as measured by accelerated thrombin generation, and enhancement of RBC-endothelial cells adhesion and RBC-RBC aggregation. Confirming the procoagulant activation of RBC in vitro, exposure to TiO2 NPs (2 mg/kg intravenously injection) in rats increased thrombus formation in the venous thrombosis model. Collectively, these results suggest that anatase TiO2 NPs may harbor prothrombotic risks by promoting the procoagulant activity of RBCs, which needs attention for its biomedical application. The online version contains supplementary material available at 10.1186/s12989-021-00422-1.
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