title: Effects of TiO₂ and Co₃O₄ nanoparticles on circulating angiogenic cells.
abstract: OBJECTIVE
  Sparse evidence suggests a possible link between exposure to airborne nanoparticles (NPs) and cardiovascular (CV) risk, perhaps through mechanisms involving oxidative stress and inflammation. We assessed the effects of TiO2 and Co3O4 NPs in human circulating angiogenic cells (CACs), which take part in vascular endothelium repair/replacement.
  
  
  METHODS
  CACs were isolated from healthy donors' buffy coats after culturing lymphomonocytes on fibronectin-coated dishes in endothelial medium for 7 days. CACs were pre-incubated with increasing concentration of TiO2 and Co3O4 (from 1 to 100 μg/ml) to test the effects of NP – characterized by Transmission Electron Microscopy – on CAC viability, apoptosis (caspase 3/7 activation), function (fibronectin adhesion assay), oxidative stress and inflammatory cytokine gene expression.
  
  
  RESULTS
  Neither oxidative stress nor cell death were associated with exposure to TiO2 NP (except at the highest concentration tested), which, however, induced a higher pro-inflammatory effect compared to Co3O4 NPs (p<0.01). Exposure to Co3O4 NPs significantly reduced cell viability (p<0.01) and increased caspase activity (p<0.01), lipid peroxidation end-products (p<0.05) and pro-inflammatory cytokine gene expression (p<0.05 or lower). Notably, CAC functional activity was impaired after exposure to both TiO2 (p<0.05 or lower) and Co3O4 (p<0.01) NPs.
  
  
  CONCLUSIONS
  In vitro exposure to TiO2 and Co3O4 NPs exerts detrimental effects on CAC viability and function, possibly mediated by accelerated apoptosis, increased oxidant stress (Co3O4 NPs only) and enhancement of inflammatory pathways (both TiO2 and Co3O4 NPs). Such adverse effects may be relevant for a potential role of exposure to TiO2 and Co3O4 NPs in enhancing CV risk in humans.
authors: Department of Clinical and Experimental Medicine. Division of Endocrinology. University of Parma and Azienda Ospedaliero-Universitaria of Parma, Parma, Italy.
authors: Valentina
authors: V
authors: Spigoni
authors: Department of Clinical and Experimental Medicine. Division of Endocrinology. University of Parma and Azienda Ospedaliero-Universitaria of Parma, Parma, Italy.
authors: Monia
authors: M
authors: Cito
authors: Department of Clinical and Experimental Medicine. Unit of Occupational and Environmental Medicine. University of Parma, Parma, Italy.
authors: Rossella
authors: R
authors: Alinovi
authors: Department of Clinical and Experimental Medicine. Unit of Occupational and Environmental Medicine. University of Parma, Parma, Italy.
authors: Silvana
authors: S
authors: Pinelli
authors: Department of Clinical and Experimental Medicine. Unit of Andrology, Metabolic Bone Diseases and Endocrinology. University of Parma, Parma, Italy.
authors: Giovanni
authors: G
authors: Passeri
authors: Department of Clinical and Experimental Medicine. Unit of Diabetes and prevention of associated diseases. University of Parma, Parma, Italy.
authors: Ivana
authors: I
authors: Zavaroni
authors: Department of Clinical and Experimental Medicine. Unit of Occupational and Environmental Medicine. University of Parma, Parma, Italy.
authors: Matteo
authors: M
authors: Goldoni
authors: IMEM-CNR (Istituto Materiale per l'Elettronica ed il Magnetismo - Consiglio Nazionale delle Ricerche) Institute, Parma, Italy.
authors: Marco
authors: M
authors: Campanini
authors: Department of Physics and Earth Sciences. University of Parma, Parma, Italy.
authors: Irene
authors: I
authors: Aliatis
authors: Department of Clinical and Experimental Medicine. Unit of Occupational and Environmental Medicine. University of Parma, Parma, Italy.
authors: Antonio
authors: A
authors: Mutti
authors: Department of Clinical and Experimental Medicine. Division of Endocrinology. University of Parma and Azienda Ospedaliero-Universitaria of Parma, Parma, Italy.
authors: Riccardo C
authors: RC
authors: Bonadonna
authors: Department of Clinical and Experimental Medicine. Division of Endocrinology. University of Parma and Azienda Ospedaliero-Universitaria of Parma, Parma, Italy.
authors: Alessandra
authors: A
authors: Dei Cas
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D003035:Cobalt / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D046529:Microscopy, Electron, Transmission; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D010087:Oxides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D061251:Primary Cell Culture; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D010087:Oxides; C009495:titanium dioxide; D003035:Cobalt; D014025:Titanium; C060728:cobalt oxide