Chapter 5: The Effects of Engineered Nanomaterials on Cultured Endothelial Cells
The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any agency determination or policy.
The vascular endothelium forms the inner lining of the vasculature and is an essential system in multicellular organisms that delivers nutrients and oxygen, removes CO2 and waste products, and facilitates interorgan communication. Endothelial dysfunctions may lead to life-threatening vascular disorders, including hypoperfusion and organ damage, and thrombotic and/or bleeding pathologies. As various engineered nanomaterials are being designed for biomedical applications for intravascular use and other nanomaterials may reach the vasculature as a result of occupational, environmental, or other types of exposure, it is necessary to evaluate the effects of engineered nanomaterials on the vascular endothelium. In the introduction of this chapter, the physiology of endothelial cells (ECs) and the pathophysiology of the possible adverse effects of nanomaterials on ECs are briefly described. Next, the methods that are used for the in vitro evaluation of the effects of nanomaterials on ECs are reviewed. Investigations of the effects of nanomaterials on ECs are primarily based on the observation of structural and functional changes in the different types of cultured ECs upon (usually) short-term exposure (up to 72 h) to various doses of nanomaterials. Numerous microscopic methods are employed to study morphological and structural changes of ECs and nanomaterial uptake. Different cell biology assays are used to assess the cytotoxicity of nanomaterials and their effects on proliferation and induction of apoptosis, necrosis, and autophagy. In addition, assays of various EC activation markers, nitric oxide (NO) and reactive oxygen species (ROS) production or functional EC mobility and morphogenesis, monolayer permeability, and vasoactivity assays also provide valuable information on nanomaterial effects on the vascular intima. Lastly, a summary of the published results regarding the in vitro effects of various nanomaterials on ECs, as well as selected assay protocols used in our laboratory are presented.
