Correction to“Inhaled Nanoparticles Accumulate at Sites of Vascular Disease”

Miller, Mark R.; Raftis, Jennifer; Langrish, Jeremy P.; McLean, Susannah; Samutrtai, Pawitrabhorn; Connell, Shea P.; Wilson, Simon; Vesey, Alex; Fokkens, Paul; Boere, A. John F.; Krystek, Petra; Campbell, Colin J.; Hadoke, Patrick W. F.; Donaldson, Ken; Cassee, Flemming R.; Newby, David E.; Duffin, Rodger; Mills, Nicholas L

doi:10.1021/acsnano.7b06327

Cited by 26 publications

(12 citation statements)

References 16 publications

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“…In vivo pulmonary exposure to B[ a ]P-coated soot particles showed that 30% of the deposited particle-bound PAH was cleared into the blood within minutes after exposure [ 17 ]. By comparison, only 0.02% of inhaled nano-sized gold particles translocated from the lung into circulation [ 80 , 81 ]. It therefore seems likely that the release of organic chemicals from DEPs deposited in the airways (on the epithelial surface) may represents a more important route of endothelial exposure, rather than direct exposure to DEPs (i.e., translocation of particles).…”

Section: Discussionmentioning

confidence: 99%

Lipophilic Chemicals from Diesel Exhaust Particles Trigger Calcium Response in Human Endothelial Cells via Aryl Hydrocarbon Receptor Non-Genomic Signalling

Brinchmann

Ferrec

Podechard

et al. 2018

IJMS

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Exposure to diesel exhaust particles (DEPs) affects endothelial function and may contribute to the development of atherosclerosis and vasomotor dysfunction. As intracellular calcium concentration [Ca2+]i is considered important in myoendothelial signalling, we explored the effects of extractable organic matter from DEPs (DEP-EOM) on [Ca2+]i and membrane microstructure in endothelial cells. DEP-EOM of increasing polarity was obtained by pressurized sequential extraction of DEPs with n-hexane (n-Hex-EOM), dichloromethane (DCM-EOM), methanol, and water. Chemical analysis revealed that the majority of organic matter was extracted by the n-Hex- and DCM-EOM, with polycyclic aromatic hydrocarbons primarily occurring in n-Hex-EOM. The concentration of calcium was measured in human microvascular endothelial cells (HMEC-1) using micro-spectrofluorometry. The lipophilic n-Hex-EOM and DCM-EOM, but not the more polar methanol- and water-soluble extracts, induced rapid [Ca2+]i increases in HMEC-1. n-Hex-EOM triggered [Ca2+]i increase from intracellular stores, followed by extracellular calcium influx consistent with store operated calcium entry (SOCE). By contrast, the less lipophilic DCM-EOM triggered [Ca2+]i increase via extracellular influx alone, resembling receptor operated calcium entry (ROCE). Both extracts increased [Ca2+]i via aryl hydrocarbon receptor (AhR) non-genomic signalling, verified by pharmacological inhibition and RNA-interference. Moreover, DCM-EOM appeared to induce an AhR-dependent reduction in the global plasma membrane order, as visualized by confocal fluorescence microscopy. DCM-EOM-triggered [Ca2+]i increase and membrane alterations were attenuated by the membrane stabilizing lipid cholesterol. In conclusion, lipophilic constituents of DEPs extracted by n-hexane and DCM seem to induce rapid AhR-dependent [Ca2+]i increase in HMEC-1 endothelial cells, possibly involving both ROCE and SOCE-mediated mechanisms. The semi-lipophilic fraction extracted by DCM also caused an AhR-dependent reduction in global membrane order, which appeared to be connected to the [Ca2+]i increase.

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Section: Discussionmentioning

confidence: 99%

Lipophilic Chemicals from Diesel Exhaust Particles Trigger Calcium Response in Human Endothelial Cells via Aryl Hydrocarbon Receptor Non-Genomic Signalling

Brinchmann

Ferrec

Podechard

et al. 2018

IJMS

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“…However, experimental studies using model nanoparticles such as radiolabelled carbon or gold nanoparticles have robustly demonstrated that this pathway occurs in rodents (Geiser & Kreyling, ) and now recently in humans (Miller et al . , b ). The translocation pathway is of importance as it provides a biological basis that could account for the widespread effects of inhaled PM across the CVS, and elsewhere in the body (Raftis & Miller, ).…”

Section: Introductionmentioning

confidence: 99%

Polyaromatic hydrocarbons in pollution: a heart‐breaking matter

Marris

Kompella

Miller

et al. 2020

The Journal of Physiology

108

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Air pollution is associated with detrimental effects on human health, including decreased cardiovascular function. However, the causative mechanisms behind these effects have yet to be fully elucidated. Here we review the current epidemiological, clinical and experimental evidence linking pollution with cardiovascular dysfunction. Our focus is on particulate matter (PM) and the associated low molecular weight polycyclic aromatic hydrocarbons (PAHs) as key mediators of cardiotoxicity. We begin by reviewing the growing epidemiological evidence linking air pollution to cardiovascular dysfunction in humans. We next address the pollution‐based cardiotoxic mechanisms first identified in fish following the release of large quantities of PAHs into the marine environment from point oil spills (e.g. Deepwater Horizon). We finish by discussing the current state of mechanistic knowledge linking PM and PAH exposure to mammalian cardiovascular patho‐physiologies such as atherosclerosis, cardiac hypertrophy, arrhythmias, contractile dysfunction and the underlying alterations in gene regulation. Our aim is to show conservation of toxicant pathways and cellular targets across vertebrate hearts to allow a broad framework of the global problem of cardiotoxic pollution to be established. AhR; Aryl hydrocarbon receptor. Dark lines indicate topics discussed in this review. Grey lines indicate topics reviewed elsewhere.

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“…Transport of NPs across biological barriers has been observed by elemental analysis in both rodents and humans [7][8][9][10][11]. As an example, gold NPs have been reported to reach the systemic circulation in humans, after inhalation, and translocate to other organs [8,9].Several in vivo studies show that NPs accumulate in the liver, which is an important target organ for NPs and other xenobiotics due to its metabolic activity [12][13][14][15][16][17][18]. Induction of hepatotoxicity is one of the most common reasons for a medicine to be rejected or removed from the market [19,20].…”

mentioning

confidence: 99%

“…Thus, humans are likely to be exposed to NPs, either intentionally or accidentally, during production and usage [6]. Transport of NPs across biological barriers has been observed by elemental analysis in both rodents and humans [7][8][9][10][11]. As an example, gold NPs have been reported to reach the systemic circulation in humans, after inhalation, and translocate to other organs [8,9].…”

mentioning

confidence: 99%

Hepato(Geno)Toxicity Assessment of Nanoparticles in a HepG2 Liver Spheroid Model

et al. 2020

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1) In compliance with the 3Rs policy to reduce, refine and replace animal experiments, the development of advanced in vitro models is needed for nanotoxicity assessment. Cells cultivated in 3D resemble organ structures better than 2D cultures. This study aims to compare cytotoxic and genotoxic responses induced by titanium dioxide (TiO 2 ), silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) in 2D monolayer and 3D spheroid cultures of HepG2 human liver cells. (2) NPs were characterized by electron microscopy, dynamic light scattering, laser Doppler anemometry, UV-vis spectroscopy and mass spectrometry. Cytotoxicity was investigated by the alamarBlue assay and confocal microscopy in HepG2 monolayer and spheroid cultures after 24 h of NP exposure. DNA damage (strand breaks and oxidized base lesions) was measured by the comet assay. (3) Ag-NPs were aggregated at 24 h, and a substantial part of the ZnO-NPs was dissolved in culture medium. Ag-NPs induced stronger cytotoxicity in 2D cultures (EC 50 3.8 µg/cm 2 ) than in 3D cultures (EC 50 > 30 µg/cm 2 ), and ZnO-NPs induced cytotoxicity to a similar extent in both models (EC 50 10.1-16.2 µg/cm 2 ). Agand ZnO-NPs showed a concentration-dependent genotoxic effect, but the effect was not statistically significant. TiO 2 -NPs showed no toxicity (EC 50 > 75 µg/cm 2 ). (4) This study shows that the HepG2 spheroid model is a promising advanced in vitro model for toxicity assessment of NPs.Nanomaterials 2020, 10, 545 2 of 21 and silver (Ag) is used as a disinfection agent in medical equipment and consumer products, on account of its antimicrobial activity [5]. Thus, humans are likely to be exposed to NPs, either intentionally or accidentally, during production and usage [6]. Transport of NPs across biological barriers has been observed by elemental analysis in both rodents and humans [7][8][9][10][11]. As an example, gold NPs have been reported to reach the systemic circulation in humans, after inhalation, and translocate to other organs [8,9].Several in vivo studies show that NPs accumulate in the liver, which is an important target organ for NPs and other xenobiotics due to its metabolic activity [12][13][14][15][16][17][18]. Induction of hepatotoxicity is one of the most common reasons for a medicine to be rejected or removed from the market [19,20]. Therefore, there is a need for sensitive hepatotoxicity screening methods for drug development and hazard assessment of chemicals or new materials, such as NPs. When considering the 3Rs-replacement, reduction and refinement-to minimize the use of animal experiments, hepatotoxicity should be assessed by reliable in vitro models. A great advantage of in vitro hepatocellular models for studying hepatotoxicity is the possibility of using human cells, either as primary cells or cell lines. The use of human hepatocyte cell lines, such as HepG2, C3A, Huh7 and HepaRG, has many advantages compared to primary cells. They are relatively easy to culture and have an unlimited life span, a relatively stable phenotype, high availability and ...

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Correction to“Inhaled Nanoparticles Accumulate at Sites of Vascular Disease”

Cited by 26 publications

References 16 publications

Lipophilic Chemicals from Diesel Exhaust Particles Trigger Calcium Response in Human Endothelial Cells via Aryl Hydrocarbon Receptor Non-Genomic Signalling

Lipophilic Chemicals from Diesel Exhaust Particles Trigger Calcium Response in Human Endothelial Cells via Aryl Hydrocarbon Receptor Non-Genomic Signalling

Polyaromatic hydrocarbons in pollution: a heart‐breaking matter

Hepato(Geno)Toxicity Assessment of Nanoparticles in a HepG2 Liver Spheroid Model

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