POSTER ABSTRACT / DETAILS:
Fullerenes are a class of nanomaterial that fully consist of carbon atoms, taking the form of a hollow, spherical shape. Because fullerenes are hypothesized to be applied in the future clinic as drug delivery agents or as a diagnostic tool it is important to assess and understand their possible toxicological effects, especially when applied internally. Upon intravenous injection, the particles will encounter vascular endothelial cells, which provide a barrier between the blood and tissues all across the cardiovascular system. Vascular endothelial cells play a crucial role in maintaining blood vessel homeostasis and thereby are also essential to prevent atherosclerosis, which is still a leading cause of death worldwide.
Here, we aimed to unravel the toxicological effects of fullerenes on vascular endothelial cells and investigate underlying biological mechanisms, using previously published microarray data (1). Several systems biology tools were used, including PathVisio, WikiPathways and Cytoscape (2, 3). We show that in reponse to fullerenes, vascular endothelial cells alter their gene expression profile to a situation in which intracellular cholesterol production, collection and preservation seem to be the ultimate goals. As expected, this situation was suggested to be caused by the activation of SREBF1 and/or SREBF2, which are two transcription factors known to regulate intracellular lipid concentrations. How exactly fullerenes are able to activate SREBF1 and SREBF2 and subsequently upregulate cholesterol synthesis remains speculative.
Previously, Hassan et al. described that during atherosclerosis onset endothelial cells are able to remain homeostatic by shutting down intracellular cholesterol synthesis and reduction of cholesterol scavengers, in this way remaining atheroprotective (4). Our results suggest that introduction of fullerenes could lead to disruption of this process and thus worsen atherosclerotic onset. We propose that the toxicological effects of fullerenes in endothelial cells are explored in more detail and validate that cholesterol levels are indeed increased. Furthermore, potential clinical use should take caution when introducing fullerenes into the vascular system of humans prone to developing atherosclerosis.
1. Yamawaki H, Iwai N. Cytotoxicity of water-soluble fullerene in vascular endothelial cells. American journal of physiology Cell physiology. 2006;290(6):C1495-502.
2. Kelder T, van Iersel MP, Hanspers K, et al. WikiPathways: building research communities on biological pathways. Nucleic acids research. 2012;40(Database issue):D1301-7.
3. van Iersel MP, Kelder T, Pico AR, et al. Presenting and exploring biological pathways with PathVisio. BMC bioinformatics. 2008;9:399.
4. Hassan HH, Denis M, Krimbou L, et al. Cellular cholesterol homeostasis in vascular endothelial cells. The Canadian journal of cardiology. 2006;22 Suppl B:35B-40B.