Several epidemiological studies have revealed the involvement of nanoparticles (NPs) in respiratory and cardiovascular mortality. In this work, the focus will be on the effect of manufactured carbon black NPs for risk assessment of consumers and workers, as human exposure is likely to increase. Since the pulmonary circulation could be one of the primary targets of inhaled NPs, patients suffering from pulmonary hypertension (PH) could be a population at risk. To compare the toxic effect of carbon black NPs in the pulmonary circulation under physiologic and pathological conditions, we developed a new in vitro model mimicking the endothelial dysfunction and vascular dynamics observed in vascular pathology such as PH. Human pulmonary artery endothelial cells were cultured under physiological conditions (static and normoxia 21% O₂) or under pathological conditions (20% cycle stretch and hypoxia 1% O₂). Then, cells were treated for 4 or 6 h with carbon black FW2 NPs from 5 to 10 µg/cm². Different endpoints were studied: (i) NPs internalization by transmission electronic microscopy; (ii) oxidative stress by CM-H₂DCFDA probe and electron paramagnetic resonance; (iii) NO (nitrites and nitrates) production by Griess reaction; (iv) inflammation by ELISA assay; and (v) calcium signaling by confocal microscopy. The present study characterizes the in vitro model mimicking endothelial dysfunction in PH and indicates that, under such pathological conditions, oxidative stress and inflammation are increased along with calcium signaling alterations, as compared to the physiological conditions. Human exposure to carbon black NPs could produce greater deleterious effects in vulnerable patients suffering from cardiovascular diseases.

几项流行病学研究表明，纳米颗粒 (NPs) 与呼吸系统和心血管死亡率有关。在这项工作中，重点将放在制造炭黑 NP 对消费者和工人风险评估的影响，因为人类接触可能会增加。由于肺循环可能是吸入 NPs 的主要目标之一，因此患有肺动脉高压 (PH) 的患者可能是处于危险中的人群。为了比较在生理和病理条件下炭黑 NPs 在肺循环中的毒性作用，我们开发了一种新的体外模型，模拟在血管病理学（例如 PH）中观察到的内皮功能障碍和血管动力学。人肺动脉内皮细胞在生理条件下（静态和常氧 21% O_{2 ）或在病理条件下（20% 循环拉伸和 1% O 2}缺氧）。^{然后，用 5 至 10 µg/cm 2}的炭黑 FW2 NP 处理细胞 4 或 6 小时。研究了不同的终点：（i）通过透射电子显微镜观察 NPs 内化；(ii) CM-H _{2的氧化应激}DCFDA探针和电子顺磁共振；(iii) 通过 Griess 反应产生 NO（亚硝酸盐和硝酸盐）；(iv) ELISA 测定的炎症；(v) 共聚焦显微镜的钙信号。本研究描述了模拟 PH 中内皮功能障碍的体外模型，并表明在这种病理条件下，与生理条件相比，氧化应激和炎症随着钙信号的改变而增加。人体接触炭黑 NP 可能会对患有心血管疾病的脆弱患者产生更大的有害影响。