Polyacrylic acid coated nanoparticles elicit endothelial cell apoptosis and diminish vascular relaxation in ex vivo perfused iliac arteries of the cane toad (Rhinella marina)
Polyacrylic acid coated nanoparticles elicit endothelial cell apoptosis and diminish vascular relaxation in ex vivo perfused iliac arteries of the cane toad (Rhinella marina)
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DOI：
10.1039/d0en00229a
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发表时间：
2020-07
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影响因子：
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通讯作者：
V. A. Ortega;Melissa S. Cameron;J. Stafford;G. Goss;J. Donald;A. Schultz
中科院分区：
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作者：
V. A. Ortega;Melissa S. Cameron;J. Stafford;G. Goss;J. Donald;A. Schultz
穿透动物外部保护屏障的纳米颗粒（NP）通过循环系统运输并分布到各种组织和器官。虽然NP对靶器官的作用受到了很大关注，但令人惊讶的是，很少有研究调查对血管系统本身的影响，尽管它在运输红细胞和白色血细胞、营养物质以及协调许多生理反应（如免疫力和应激）中起着关键作用。在这项研究中，我们用聚丙烯酸（PAA）涂层的TiO 2纳米颗粒（3-9 nm）灌注从甘蔗蟾蜍（Rhinella marina）提取的髂动脉，以直接评估对跨管腔内皮层摄取的影响，血管生理功能的变化和毒性。用400 μg mL−1 PAA-TiO 2 NP灌注髂动脉导致血管内皮层的组织病理学变化，这是由于通过凋亡增加了内皮细胞死亡。观察到PAA-NP穿透至少两个细胞层，并且存在于内皮细胞和下面的平滑肌细胞中。双丝肌电实验显示，最高剂量的PAA-TiO 2纳米颗粒显著抑制血管中ACh介导的血管舒张达50%，这似乎是由于血管内腔中的内皮层受损。这是第一项使用体外灌注方法的研究，该方法模拟血液循环，结合双线肌造影术，以证明NP对血管生理学的不良影响。
Nanoparticles (NP) that penetrate external protective barriers of an animal are transported and distributed to various tissues and organs via the circulatory system. Whilst much attention has been dedicated to NP effects on target organs, surprisingly few studies have investigated effects on the vascular system itself, despite the critical role it plays in transporting red and white blood cells, nutrients, as well as coordinating many physiological responses, like immunity and stress. In this study we perfused iliac arteries extracted from cane toads (Rhinella marina) with polyacrylic acid (PAA) coated TiO2 NPs (3–9 nm) to directly assess effects on uptake across luminal endothelial layers, changes to vessel physiological function and toxicity. Perfusion of the iliac artery with 400 μg mL−1 PAA-TiO2 NPs resulted in histopathological changes in the vascular endothelial layer due to increased endothelial cell death via apoptosis. The PAA-NPs were observed to penetrate at least two cell layers and were present in both endothelial cells and underlying smooth muscle cells. Dual-wire myography experiments revealed that the highest dose of PAA-TiO2 NPs significantly inhibited the ACh-mediated vasodilation in blood vessels by ∼50%, which appeared to be attributable to the damaged endothelial layer in the lumen of the vessels. This is the first study to use an ex vivo perfusion method that mimics the blood circulation coupled with dual-wire myography to demonstrate the adverse effects of NPs on blood vessel physiology.