Department of Public Health, Section of Environmental Health, University of Copenhagen, Øster Farimagsgade 5A, DK-1014 Copenhagen K, Denmark.
Crit Rev Toxicol. 2011 Apr;41(4):339-68. doi: 10.3109/10408444.2010.533152. Epub 2011 Feb 24.
The development and use of nanoparticles have alerted toxicologists and regulators to issues of safety testing. By analogy with ambient air particles, it can be expected that small doses are associated with a small increase in risk of cardiovascular diseases, possibly through oxidative stress and inflammatory pathways. We have assessed the effect of exposure to particulate matter on progression of atherosclerosis and vasomotor function in humans, animals, and ex vivo experimental systems. The type of particles that have been tested in these systems encompass TiO(2), carbon black, fullerene C(60), single-walled carbon nanotubes, ambient air particles, and diesel exhaust particles. Exposure to ambient air particles is associated with accelerated progression of atherosclerosis and vasomotor dysfunction in both healthy and susceptible animal models and humans at risk of developing cardiovascular diseases. The vasomotor dysfunction includes increased vasoconstriction as well as reduced endothelium-dependent vasodilatation; endothelium-independent vasodilatation is often unaffected indicating mainly endothelial dysfunction. Pulmonary exposure to TiO(2), carbon black, and engineered nanoparticles generate vasomotor dysfunction; the effect size is similar to that generated by combustion-derived particles, although the effect could depend on the exposure period and the administered dose, route, and mode. The relative risk associated with exposure to nanoparticles may be small compared to some traditional risk factors for cardiovascular diseases, but superimposed on these and possible exposure to large parts of the population it is a significant public health concern. Overall, assessment of vasomotor dysfunction and progression of atherosclerosis are promising tools for understanding the effects of particulate matter.
纳米颗粒的开发和使用引起了毒理学家和监管机构对安全测试问题的关注。类比于环境空气中的颗粒，可以预期小剂量与心血管疾病风险的微小增加有关，可能通过氧化应激和炎症途径。我们评估了暴露于颗粒物对人类、动物和离体实验系统中动脉粥样硬化进展和血管舒缩功能的影响。在这些系统中测试的颗粒类型包括 TiO(2)、炭黑、富勒烯 C(60)、单壁碳纳米管、环境空气颗粒和柴油废气颗粒。暴露于环境空气颗粒与在健康和易感动物模型以及易患心血管疾病的人群中加速动脉粥样硬化进展和血管舒缩功能障碍有关。血管舒缩功能障碍包括血管收缩增加以及内皮依赖性血管舒张减少；内皮非依赖性血管舒张通常不受影响，表明主要是内皮功能障碍。肺部暴露于 TiO(2)、炭黑和工程纳米颗粒会引起血管舒缩功能障碍；其作用大小与燃烧衍生颗粒产生的作用大小相似，尽管作用可能取决于暴露期、施用剂量、途径和模式。与暴露于纳米颗粒相关的相对风险可能比心血管疾病的一些传统危险因素小，但与这些危险因素叠加，并且可能暴露于大部分人群中，这是一个重大的公共卫生问题。总的来说，评估血管舒缩功能障碍和动脉粥样硬化进展是了解颗粒物影响的有前途的工具。
