Abstract
Tubular nanomaterials (NMs), such as multi-walled carbon nanotubes (MWCNTs) and halloysite nanotubes (HNTs), may be used in biomedicine, but previous studies showed that MWCNTs induced toxicity to endothelial cells (ECs). However, the influence of tubular NMs on EC lipid profiles has gained little attention, probably because ECs are not traditionally considered to be involved in regulating lipid homeostasis. This study compared the different effects of MWCNTs and HNTs on lipid profile changes in human umbilical vein ECs (HUVECs). The results showed that MWCNTs but not HNTs of the same mass concentrations induced cytotoxicity, ultrastuctural changes and intracellular thiol depletion. Meanwhile, only MWCNTs promoted lipid accumulation due to the induction of ER stress leading to up-regulation of fatty acid synthase (FASN). Interestingly, lipidomics results showed that the main lipid classes induced by MWCNTs but not HNTs were ceramide (Cer) and phosphatidylinositol (PI), with most of the lipid classes unaltered or even decreased after NM exposure. Then, extra Cer and PI were added to explore the implications of increase of these lipids. Adding Cer promoted the cytotoxicity of MWCNTs to HUVECs, indicating the lipotoxic role of Cer. Whereas adding PI partially increased intracellular NO and decreased interleukin-6 (IL-6) release due to MWCNT exposure, indicating the signaling role of PI. These results indicated novel roles of lipid dysfunction in NM-induced toxicity to ECs, even though ECs are not the professional cells for controlling lipid homeostasis.