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Effects of FW2 Nanoparticles Toxicity in a New In Vitro Pulmonary Vascular Cells Model Mimicking Endothelial Dysfunction

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Abstract

Several epidemiological studies have revealed the involvement of nanoparticles (NPs) in respiratory and cardiovascular mortality. In this work, the focus will be on the effect of manufactured carbon black NPs for risk assessment of consumers and workers, as human exposure is likely to increase. Since the pulmonary circulation could be one of the primary targets of inhaled NPs, patients suffering from pulmonary hypertension (PH) could be a population at risk. To compare the toxic effect of carbon black NPs in the pulmonary circulation under physiologic and pathological conditions, we developed a new in vitro model mimicking the endothelial dysfunction and vascular dynamics observed in vascular pathology such as PH. Human pulmonary artery endothelial cells were cultured under physiological conditions (static and normoxia 21% O2) or under pathological conditions (20% cycle stretch and hypoxia 1% O2). Then, cells were treated for 4 or 6 h with carbon black FW2 NPs from 5 to 10 µg/cm2. Different endpoints were studied: (i) NPs internalization by transmission electronic microscopy; (ii) oxidative stress by CM-H2DCFDA probe and electron paramagnetic resonance; (iii) NO (nitrites and nitrates) production by Griess reaction; (iv) inflammation by ELISA assay; and (v) calcium signaling by confocal microscopy. The present study characterizes the in vitro model mimicking endothelial dysfunction in PH and indicates that, under such pathological conditions, oxidative stress and inflammation are increased along with calcium signaling alterations, as compared to the physiological conditions. Human exposure to carbon black NPs could produce greater deleterious effects in vulnerable patients suffering from cardiovascular diseases.

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Abbreviations

CS:

Cyclic stretch

EC:

Endothelial cells

HPAEC:

Human pulmonary artery endothelial cells

NPs:

Nanoparticles

PH:

Pulmonary human

ROS:

Reactive oxygen species

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Acknowledgements

The PhD scholarship of Juliette DEWEIRDT was provided by the “Fondation pour la Recherche Médicale”—FRM PMJ20151034585.

Funding

This work was supported by the "Fonds de Dotation pour la Recherche en Santé Respiratoire" (Grant 2012/2013).

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Authors and Affiliations

  1. University of Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, U 1045, 33000, Bordeaux, France

    J. Deweirdt, T. Ducret, J.-F. Quignard, V. Freund-Michel, B. Muller, R. Marthan, C. Guibert & I. Baudrimont

  2. Inserm U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, 33604, Pessac, France

    J. Deweirdt, T. Ducret, J.-F. Quignard, V. Freund-Michel, B. Muller, R. Marthan, C. Guibert & I. Baudrimont

  3. CNRS, Bordeaux Imaging Center UMS 3420 CNRS – US4 INSERM, 33000, Bordeaux, France

    S. Lacomme & E. Gontier

  4. CHU de Bordeaux, Service d’Exploration Fonctionnelle Respiratoire, 33000, Bordeaux, France

    R. Marthan

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  1. J. Deweirdt
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  2. T. Ducret
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  4. V. Freund-Michel
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  9. C. Guibert
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  10. I. Baudrimont
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Correspondence to I. Baudrimont.

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Deweirdt, J., Ducret, T., Quignard, JF. et al. Effects of FW2 Nanoparticles Toxicity in a New In Vitro Pulmonary Vascular Cells Model Mimicking Endothelial Dysfunction. Cardiovasc Toxicol 22, 14–28 (2022). https://doi.org/10.1007/s12012-021-09679-6

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