Commercial single-walled carbon nanotubes effects in fibrinolysis of human umbilical vein endothelial cells

• Published in: Toxicology in vitro Vol. 29; no. 5; pp. 1201 - 1214
• Main Authors: Rodríguez-Yáñez, Yury, Bahena-Uribe, Daniel, Chávez-Munguía, Bibiana, López-Marure, Rebeca, González-Monroy, Stuart, Cisneros, Bulmaro, Albores, Arnulfo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2015
• Subjects: Cells, Cultured; Commercial carbon nanotubes; Endothelial cells; Fibrinolysis; Fibrinolysis - drug effects; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Nanotubes, Carbon - toxicity; Oxidative stress; Plasminogen Activator Inhibitor 1 - metabolism; Tissue Plasminogen Activator - metabolism; Urokinase-Type Plasminogen Activator - metabolism; Oxidative stress; KLK1; DTT; H2DCFDA; FS; HR-TEM; ECs; CNTs; FBS; HUVEC; PAI-1; cDNA; PAs; tPA; SWCNTs; uPA; Fibrinolysis; Endothelial cells; KKS; TNF-α; C-TEM; ROS; Commercial carbon nanotubes; PI; MWCNTs; PCR; ELISA
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2015.02.009

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•Pristine-commercial SWCNTs are oxidants and produce oxidative stress.•SWCNTs were internalized in HUVEC and caused cytotoxicity.•Fibrinolysis-related gene expression and proteins were affected by commercial SWCNTs.•Cobalt content and physical interference of SWCNTs influence the cell response.•Commercial SWCNT-induced alterations to fibrinolysis system may produce a pro-thrombotic effect.
Recent studies have demonstrated that carbon nanotubes (CNTs) induce platelet aggregation, endothelial dysfunction and vascular thrombosis. However, there is little information on the effects of CNTs on fibrinolysis. We investigated the role of pristine-commercial single-walled carbon nanotubes (SWCNTs) with <3% Co content in fibrinolysis and their contribution to the induction of pro-thrombotic processes in human vein endothelial cells (HUVEC). SWCNTs alone produced concentration-dependent oxidation, as measured by a dithiothreitol oxidation assay. Internalized SWCNTs were located in HUVEC treated with 25μg/ml using transmission electron microscopy, whereas treatment with 50μg/ml compromised cell viability, and oxidative stress increased significantly at 5μg/ml. The study showed that in HUVEC treated with 25μg SWCNT/ml, fibrinolysis-related gene expression and protein levels had increased by 3–12h after treatment (serpine-1: 13-fold; PLAT: 11-fold and PLAU: 2-fold), but only the PAI-1 protein was increased (1.5-fold), whereas tissue and urokinase plasminogen activator proteins (tPA and uPA, respectively) tended to decrease. In summary, pristine SWCNTs treatment resulted in evident HUVEC damage caused by cell fiber contact, internalization, and oxidative stress due to contaminant metals. The generation of endothelial dysfunction, as shown by the altered expression of genes and proteins involved in fibrinolysis, suggest that SWCNTs display pro-thrombotic effects.