Key Laboratory for Deep Processing of Major Grain and Oil (Wuhan Polytechnic University), Ministry of Education, College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan, 430023, People's Republic of China.
Department of Biomedical Engineering, School of Engineering & Applied Science, Yale University, New Haven, 06520, USA.
J Nanobiotechnology. 2019 Feb 1;17(1):20. doi: 10.1186/s12951-019-0458-2.
A growing body of evidence shows that indoor concentrations of airborne particles are often higher than is typically encountered outdoors. Since exposure to indoor PM2.5 is thought to be associated with cardiovascular disease, the health impacts of indoor air pollution need to be explored. Based on animal models, ambient particulate matter has been proved to promote coagulation which is very likely involved in the pathogenic development of cardiovascular disease. However, animal models are insufficient to predict what will happen with any certainty in humans. For this reason, the precise pathogenic mechanisms behind the development of cardiovascular disease in humans have not yet been determined.
We generated a 3D functional human microvascular network in a microfluidic device. This model enables human vascular endothelial cells to form tissue-like microvessels that behave very similarly to human blood vessels. The perfusable microvasculature allows the delivery of particles introduced into these generated human-like microvessels to follow the fluid flow. This exposure path effectively simulates the dynamic movement of airborne nanoscale particles (ANPs) within human vessels. In this study, we first identified the existence of ANPs in indoor air pollution. We then showed that ANPs could activate endothelial cells via ROS induced inflammation, and further resulted in abnormal expression of the coagulation factors (TF, TM and t-PA) involved in coagulation cascades. In addition, we found that a protein could cover ANPs, and this biointeraction could interfere with heparan sulfate (HS). Human organotypic 3D microvessel models provide a bridge for how research outcomes can translate to humans.
The 3D human microvessel model was used to determine the physiological responses of human vessels to ANP stimulation. Based on the obtained data, we concluded that ANPs not only disrupts normal coagulation functions, but also act directly on anticoagulant factors in human vessels. These experimental observations provide a potential biological explanation for the epidemiologically established link between ANPs and coagulation abnormality. This organ-on-chip model may provide a bridge from in vitro results to human responses.
越来越多的证据表明，室内空气中的悬浮颗粒物浓度通常高于室外。由于室内 PM2.5 暴露与心血管疾病有关，因此需要探索室内空气污染对健康的影响。基于动物模型，环境颗粒物已被证明可促进凝血，这很可能与心血管疾病的发病机制有关。然而，动物模型不足以确定人类一定会发生什么。出于这个原因，人类心血管疾病发病的确切致病机制仍未确定。
我们在微流控装置中生成了一个 3D 功能性人微血管网络。该模型使人类血管内皮细胞能够形成类似组织的微血管，其行为与人类血管非常相似。可灌注的微血管允许将引入这些生成的类人微血管的颗粒输送到这些颗粒随着流体流动。这种暴露途径有效地模拟了空气中纳米级颗粒 (ANP) 在人体血管内的动态运动。在这项研究中，我们首先在室内空气污染中确定了 ANP 的存在。然后我们表明，ANP 可以通过 ROS 诱导的炎症激活内皮细胞，进而导致涉及凝血级联的凝血因子 (TF、TM 和 t-PA) 的异常表达。此外，我们发现一种蛋白质可以覆盖 ANP，这种生物相互作用可以干扰肝素硫酸盐 (HS)。人类器官型 3D 微血管模型为研究结果如何转化为人类提供了桥梁。
使用 3D 人微血管模型来确定人血管对 ANP 刺激的生理反应。基于获得的数据，我们得出结论，ANP 不仅破坏正常的凝血功能，而且直接作用于人血管中的抗凝因子。这些实验观察结果为流行病学上建立的 ANP 与凝血异常之间的联系提供了潜在的生物学解释。这种器官芯片模型可以为从体外结果到人体反应提供桥梁。
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