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Direct and Indirect Effect of Air Particles Exposure Induce Nrf2-Dependent Cardiomyocyte Cellular Response In Vitro

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Abstract

Air particulate matter has been associated with adverse effects in the cardiorespiratory system leading to cytotoxic and pro-inflammatory effects. Particulate matter-associated cardiac effects may be direct or indirect. While direct interactions may occur when inhaled ultrafine particles and/or particle components cross the air–blood barrier reaching the cardiac tissue, indirect interactions may occur as the result of pulmonary inflammation and consequently the release of inflammatory and oxidative mediators into the blood circulation. The aim of the study is to investigate the direct or indirectly the effect of Urban Air particles from downtown Buenos Aires (UAP-BA) and residual oil fly ash (ROFA), a surrogate of ambient air pollution, on cardiomyocytes (HL-1 cells). HL-1 cultured cells were directly exposed to particulate matter [UAP-BA (10–200 µg/ml), ROFA (1–100 µg/ml)] or indirectly exposed to conditioned media (CM) from particle-exposed alveolar macrophages (AM). Metabolic activity, reactive oxygen species (ROS), and Nrf2 expression were assessed by MTT, DHR 123, and immunocytochemistry techniques, respectively. We found that direct exposure of cardiomyocytes to UAP-BA or ROFA increased ROS generation but the oxidative damage did not alter metabolic activity likely by a concomitant increase in the cytoplasmic and nuclear Nrf2 expression. However, indirect exposure through CM caused a marked reduction on cardiac metabolic activity probably due to the rise in ROS generation without Nrf2 translocation into the cell nuclei. In this in vitro model, our results indicate both direct and indirect PM effects on cardiomyocytes cells in culture. Our findings employing lung and cardiomyocytes cells provide support to the hypothesis that particle-induced cardiac alteration may possibly involve lung-derived mediators.

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Acknowledgements

The authors would like to thank Dr. W. Claycomb for the cardiomyocyte cell line and A. Perez de la Hoz for his assistance and technical expertise with the collector sampler.

Funding

This work was partially supported by Grants A147 and SJ10/54 from Universidad Nacional de San Martín Grants 2010-1661 and 2012-0328 from ANPCyT-PICT.

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Authors and Affiliations

  1. Universidad Nacional de San Martín, Escuela de Ciencia y Tecnología, Centro de Estudios en Salud y Medio Ambiente, Martín de Irigoyen 3100, 1650, San Martín, Buenos Aires, Argentina

    N. S. Orona, F. Astort, G. A. Maglione & D. R. Tasat

  2. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina

    N. S. Orona & F. Astort

  3. Universidad de Buenos Aires, Facultad de Odontología, Cátedra de Histología y Embriologia, Buenos Aires, Argentina

    G. A. Maglione & D. R. Tasat

  4. Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, VA, USA

    J. S. Yakisich

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  1. N. S. Orona
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Correspondence to N. S. Orona.

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Orona, N.S., Astort, F., Maglione, G.A. et al. Direct and Indirect Effect of Air Particles Exposure Induce Nrf2-Dependent Cardiomyocyte Cellular Response In Vitro. Cardiovasc Toxicol 19, 575–587 (2019). https://doi.org/10.1007/s12012-019-09530-z

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