title: Angiogenic effect induced by mineral fibres.
abstract: Due to the toxic effect of asbestos, other materials with similar chemical-physical characteristics have been introduced to substitute it. We evaluate the angiogenic effect of certain asbestos substitute fibres such as glass fibres (GFs), ceramic fibres (CFs) and wollastonite fibres (WFs) and then compare angiogenic responses to those induced by crocidolite asbestos fibres (AFs). An in vitro model using human endothelial cells in small islands within a culture matrix of fibroblasts (Angio-Kit) was used to evaluate vessel formation. The release of IL-6, sIL-R6, IL-8, VEGF-A and their soluble receptors, sVEGFR-1, sVEGFR-2, was determined in the conditioning medium of Angio-Kit system after fibre treatment. ROS formation and cell viability were evaluated in cultured endothelial cells (HUVEC). To evaluate the involvement of intracellular mechanisms, EGFR signalling, ROS formation and nuclear factor-κB (NFκB) pathway were then inhibited by incubating HUVEC cells with AG1478, NAC and PDTC respectively, and the cytokine and growth factor release was analyzed in the culture medium after 7 days of fibre incubation. Among the mineral fibres tested, WFs markedly induced blood vessel formation which was associated with release of IL-6 and IL-8, VEGF-A and their soluble receptors. ROS production was observed in HUVEC after WFs treatment which was associated with cell cytotoxicity. The EGFR-induced ERK phosphorylation and ROS-mediated NFκB activation were involved in the cytokine and angiogenic factor release. However, only the EGFR activation was able to induce angiogenesis. The WFs are potential angiogenic agents that can induce regenerative cytokine and angiogenic factor production resulting in the formation of new blood vessels.
authors.affiliation: Department of Molecular Pathology and Innovative Therapies, Clinic of Occupational Medicine, Polytechnic University of Marche, via Tronto 10A, 60126 Ancona, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Carbonari
authors.forename: Antonella
authors.initials: A
authors.lastname: Campopiano
authors.forename: Deborah
authors.initials: D
authors.lastname: Ramires
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Strafella
authors.forename: Sara
authors.initials: S
authors.lastname: Staffolani
authors.forename: Marco
authors.initials: M
authors.lastname: Tomasetti
authors.forename: Roberta
authors.initials: R
authors.lastname: Curini
authors.forename: Matteo
authors.initials: M
authors.lastname: Valentino
authors.forename: Lory
authors.initials: L
authors.lastname: Santarelli
authors.forename: Monica
authors.initials: M
authors.lastname: Amati
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000737:chemistry / Q000633:toxicity*; D017638:Asbestos, Crocidolite / Q000633:toxicity; D017610:Calcium Compounds / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002516:Ceramics / Q000633:toxicity; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005898:Glass; D006801:Humans; D019016:Mineral Fibers / Q000633:toxicity*; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017640:Silicates / Q000633:toxicity; D014470:Umbilical Cord; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D017610:Calcium Compounds; D016207:Cytokines; D019016:Mineral Fibers; D017382:Reactive Oxygen Species; D017640:Silicates; D042461:Vascular Endothelial Growth Factor A; C009753:fiberglass; D017638:Asbestos, Crocidolite; D066246:ErbB Receptors; C031293:calcium silicate