Vol.:(0123456789) 1 3 Cardiovascular Toxicology https://doi.org/10.1007/s12012-019-09518-9 Combustion Particle‑Induced Changes in Calcium Homeostasis: A Contributing Factor to Vascular Disease? Jørn A. Holme 1  · Bendik C. Brinchmann 1  · Eric Le Ferrec 2  · Dominique Lagadic‑Gossmann 2  · Johan Øvrevik 1,3 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Air pollution is the leading environmental risk factor for disease and premature death in the world. This is mainly due to exposure to urban air particle matter (PM), in particular, fne and ultrafne combustion-derived particles (CDP) from trafc- related air pollution. PM and CDP, including particles from diesel exhaust (DEP), and cigarette smoke have been linked to various cardiovascular diseases (CVDs) including atherosclerosis, but the underlying cellular mechanisms remain unclear. Moreover, CDP typically consist of carbon cores with a complex mixture of organic chemicals such as polycyclic aromatic hydrocarbons (PAHs) adhered. The relative contribution of the carbon core and adhered soluble components to cardiovas- cular efects of CDP is still a matter of discussion. In the present review, we summarize evidence showing that CDP afects intracellular calcium regulation, and argue that CDP-induced impairment of normal calcium control may be a critical cellular event through which CDP exposure contributes to development or exacerbation of cardiovascular disease. Furthermore, we highlight in vitro research suggesting that adhered organic chemicals such as PAHs may be key drivers of these responses. CDP, extractable organic material from CDP (CDP-EOM), and PAHs may increase intracellular calcium levels by interacting with calcium channels like transient receptor potential (TRP) channels, and receptors such as G protein-coupled receptors (GPCR; e.g., beta-adrenergic receptors [βAR] and protease-activated receptor 2 [PAR-2]) and the aryl hydrocarbon receptor (AhR). Clarifying a possible role of calcium signaling and mechanisms involved may increase our understanding of how air pollution contributes to CVD. Keywords Diesel exhaust particles · Polycyclic aromatic hydrocarbons · Endothelial dysfunction · Aryl hydrocarbon receptor · Calcium signaling Abbreviations ADRs Adrenergic receptors AhR Aryl hydrocarbon receptor ARNT AhR nuclear translocator B[a]P Benzo[a]pyrene CVD Cardiovascular diseases CDP Combustion-derived particles CYP Cytochrome P450 [Ca 2+ ] i Cytosolic concentration of calcium DEP Diesel exhaust particles DEP-EOM Extractable organic material of DEP GPCRs G protein-coupled receptors MMPs Matrix metalloproteinases NF-κB Nuclear factor-κB 1-NP 1-nitropyrene OC Organic chemicals oxLDL Oxidized low-density lipoproteins PM Particular matter PAHs Polycyclic aromatic hydrocarbons PAR-2 Protease-activated receptor 2 ROS Reactive oxygen species ROCE Receptor-operated calcium entry RTKs Receptor tyrosine kinases Handling Editor: Travis Knuckles. * Jørn A. Holme jorn.holme@fhi.no * Johan Øvrevik Johan.Ovrevik@fhi.no 1 Department of Air Pollution and Noise, Division of Infection Control, Environment and Health, Norwegian Institute of Public Health, PO Box 4404, Nydalen, 0403 Oslo, Norway 2 Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé environnement et travail) - UMR_S 1085, 35000 Rennes, France 3 Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway