title: TiO₂ nanoparticles induce dysfunction and activation of human endothelial cells.
abstract: Nanoparticles can reach the blood and cause inflammation, suggesting that nanoparticles-endothelial cells interactions may be pathogenically relevant. We evaluated the effect of titanium dioxide nanoparticles (TiO₂) on proliferation, death, and responses related with inflammatory processes such as monocytic adhesion and expression of adhesion molecules (E- and P-selectins, ICAM-1, VCAM-1, and PECAM-1) and with inflammatory molecules (tissue factor, angiotensin-II, VEGF, and oxidized LDL receptor-1) on human umbilical vein endothelial cells (HUVEC). We also evaluated the production of reactive oxygen species, nitric oxide production, and NF-κB pathway activation. Aggregates of TiO₂ of 300 nm or smaller and individual nanoparticles internalized into HUVEC inhibited proliferation strongly and induced apoptotic and necrotic death starting at 5 μg/cm². Besides, TiO₂ induced activation of HUVEC through an increase in adhesion and in expression of adhesion molecules and other molecules involved with the inflammatory process. These effects were associated with oxidative stress and NF-κB pathway activation. In conclusion, TiO₂ induced HUVEC activation, inhibition of cell proliferation with increased cell death, and oxidative stress.
authors.affiliation: Departamento de Biología Celular, Instituto Nacional de Cardiología "Ignacio Chávez", México.
authors.forename: Angélica
authors.initials: A
authors.lastname: Montiel-Dávalos
authors.forename: José Luis
authors.initials: JL
authors.lastname: Ventura-Gallegos
authors.forename: Ernesto
authors.initials: E
authors.lastname: Alfaro-Moreno
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Soria-Castro
authors.forename: Ethel
authors.initials: E
authors.lastname: García-Latorre
authors.forename: José Gerardo
authors.initials: JG
authors.lastname: Cabañas-Moreno
authors.forename: María
authors.initials: M
authors.lastname: del Pilar Ramos-Godinez
authors.forename: Rebeca
authors.initials: R
authors.lastname: López-Marure
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013925:Thromboplastin / Q000378:metabolism; D014025:Titanium / Q000737:chemistry*; D020298:U937 Cells; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D011973:Receptors, LDL; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; C009495:titanium dioxide; D013925:Thromboplastin; D014025:Titanium