Angiogenic effect induced by mineral fibres

Our plain-English summary of Angiogenic effect induced by mineral fibres, by D. Carbonari, A. Campopiano, D. Ramires, et al (Toxicology, 2011).

The study

• Authors: D. Carbonari, A. Campopiano, D. Ramires, E. Strafella, S. Staffolani, M. Tomasetti, R. Curini, M. Valentino, L. Santarelli, M. Amati
• Journal: Toxicology
• Published: 2011;288(1-3):34-42
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

In plain English

In this laboratory (cell culture) study, the authors tested whether three asbestos-substitute fibres (glass, ceramic and wollastonite) could trigger new blood-vessel formation (angiogenesis), and compared them with crocidolite asbestos. They used human endothelial cells grown among fibroblasts, and separately cultured human umbilical vein endothelial cells. Wollastonite fibres were similar in size to the crocidolite, while glass and ceramic fibres were longer and thicker. After 14 days, wollastonite markedly induced vessel networks in a similar fashion to crocidolite. Ceramic fibres did so to a lesser extent. Among the substitutes, only wollastonite increased release of IL-8 and the growth factor VEGF-A, and it also increased IL-6. Like crocidolite, wollastonite generated reactive oxygen species, which was associated with reduced cell viability. Glass and ceramic fibres showed low or no oxidative activity. Blocking the EGFR signalling pathway markedly inhibited vessel formation, while blocking oxygen radicals or the NF-kappaB pathway did not. The authors concluded that, among the substitutes, only wollastonite exerted an angiogenic effect. They suggested that in the body this may create conditions leading to disease.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: In vitro laboratory experiment (cell culture), with no human or animal subjects
• Who was studied: Two cell systems. (1) A commercial Angio-Kit, in which human endothelial cells were co-cultured with fibroblasts. (2) Cultured human umbilical vein endothelial cells (HUVEC), used for oxygen radical, viability and signalling tests. The work was done by groups in Ancona and Rome, Italy.
• Exposure: Crocidolite asbestos (UICC sample); glass fibres and ceramic fibres from two Italian manufacturers; and NYAD wollastonite fibres from an Italian fibre-reinforced cement company. Doses were 0.25 and 0.50 cm2/cm2, defined as fibre surface area relative to well surface area.
• Main results:
  • Glass and ceramic fibres were longer and thicker than crocidolite. Geometric mean lengths were 32.0 for glass, 34.3 for ceramic and 5.1 for crocidolite (p less than 0.0001). The unit symbol is garbled in the text.
  • Wollastonite fibres were similar in size to crocidolite: geometric mean length 4.8 and diameter 0.7 (unit symbol garbled in the text).
  • In the Angio-Kit model, wollastonite markedly induced formation of a vessel network after 14 days, similar to crocidolite. Tubule results came from two independent experiments performed in duplicate.
  • The higher fibre dose (0.50 cm2/cm2) did not further increase tubule density compared with the lower dose.
  • Ceramic fibres also produced tubule formation, to a lesser extent.
  • Among the substitute fibres, only wollastonite induced secretion of IL-8 and VEGF-A into the Angio-Kit medium.
  • Like crocidolite, wollastonite increased secretion of the inflammatory cytokine IL-6 compared with untreated samples.
  • All the substitute fibres tested produced a slight increase in the soluble VEGF receptors sVEGFR-1 and sVEGFR-2.
  • In a cell-free test, wollastonite produced reactive oxygen species in a similar fashion to crocidolite. Glass and ceramic fibres produced little.
  • Inside HUVEC cells, no sign of oxidative stress was detected with glass or ceramic fibres.
  • Oxygen radical formation induced by wollastonite was associated with decreased viability of HUVEC cells.
  • Blocking oxygen radicals or the NF-kappaB pathway cancelled IL-6 production in response to crocidolite and wollastonite.
  • Blocking NF-kappaB had no effect on IL-8 or VEGF-A production.
  • In the Angio-Kit (tested with crocidolite and wollastonite only), blocking oxygen radicals (NAC) or the NF-kappaB pathway (PDTC) did not inhibit vessel formation.
  • Blocking the EGFR pathway markedly inhibited vessel formation induced by crocidolite and wollastonite.
• The authors' conclusion: The authors concluded that, among the asbestos-substitute fibres, only wollastonite exerted an angiogenic effect. They attributed this to its asbestos-like characteristics, which let it interact directly with cell receptors. They suggested this may create favourable conditions that in the body could result in pathological conditions.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Wollastonite, Crocidolite, Fibroblast, EGFR, Cytokine, Angiogenesis.

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