Invited Perspective: The Silent Threat-Air Pollution's Link to Arrhythmias.

Vol. 131, No. 11 Invited PerspectiveOpen AccessInvited Perspective: The Silent Threat—Air Pollution’s Link to Arrhythmiasis accompanied byGlobal Air Pollutant Phenanthrene and Arrhythmic Outcomes in a Mouse Model Flavia Bonalumi and Michele Miragoli Flavia Bonalumi Center of Excellence for Toxicological Research (CERT), Department of Medicine and Surgery, University of Parma, Parma, Italy Search for more papers by this author and Michele Miragoli Address correspondence to Michele Miragoli, Department of Medicine and Surgery, University of Parma, Via Gramsci 14, 43124 Parma, Italy. Email: E-mail Address: [email protected] https://orcid.org/0000-0002-4058-4368 Center of Excellence for Toxicological Research (CERT), Department of Medicine and Surgery, University of Parma, Parma, Italy IRCCS Humanitas Research Hospital, Milan, Italy Search for more papers by this author Published:1 November 2023CID: 111301https://doi.org/10.1289/EHP13720AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit In today’s rapidly advancing world, marked by ever-increasing industrialization and technological progress, the implications of air pollution for human health have reached critical proportions.1 Although we have become familiar with the well-documented respiratory and cardiovascular effects of air pollution, it has become evident that the consequences of air pollution exposure extend beyond what was previously acknowledged. The impact of air pollution on cardiac health and its role in the development of arrhythmia have emerged as areas of growing concern, particularly with regard to sudden death.2Although the precise mechanisms by which air pollutants trigger arrhythmia are not yet fully understood, two primary pathways have been identified: indirect and direct. Indirect mechanisms involve the systemic inflammation caused by the inhalation of pollutants, which can promote the development of atherosclerosis, a condition characterized by the buildup of plaques in the arteries.3,4 In addition, ambient air pollution is associated with impairments in vascular function, contributing to an increased risk of cardiovascular events, including arrhythmia.5 On the other hand, direct mechanisms involve the translocation of ultrafine particulate matter (PM) from the lungs into the bloodstream,6 allowing these minuscule particles to travel to the heart and exert their deleterious effects on electromechanical coupling.7 The composition of PM varies depending on the geographical location and sources of pollution, which necessitates a comprehensive understanding of the specific PM constituents and their effect on cardiac tissue.Researchers have made strides in unraveling the intricate ways in which certain pollutants affect cardiac function. The study by Yaar et al.8 in this issue of Environmental Health Perspectives sheds light on how phenanthrene, an aromatic hydrocarbon present in PM, can disrupt heart rate, prolonging the PR interval and reducing cardiac conduction velocity. Although this study was performed ex vivo (Langerdorff perfusion on mouse hearts), in vitro (patch clamp on mouse cardiac cells), and in silico (O’Hara Rudy model), rather than in vivo, the findings highlight the alarming possibility that arrhythmia can be initiated within just 15 min of phenanthrene exposure.However, despite these discoveries, fundamental questions persist. One pressing issue is determining the threshold concentration and duration of PM exposures that lead to arrhythmia. In addition, researchers are investigating which specific pollutants act as triggers for arrhythmogenesis, and whether individual susceptibility to air pollutants and other triggers (exposure to, e.g., urban stressors, unhealthy foods, mental illness, chronic diseases, age) play a significant role in the context of sudden death.Recently, we demonstrated that diesel exhaust nanoparticles, a major component of ultrafine PM, can heighten susceptibility to arrhythmia in rats after a relatively short exposure period.7 The ability of these nanoparticles to cross the alveolar–blood barrier and interact with the cardiac membrane potential contributes to their pro-arrhythmic effects.9In addition to phenanthrene, other compounds—such as carbon monoxide, hydrogen sulfide, sulfur dioxide, ozone, and nitrogen dioxide, as well as metals—have been identified as direct pollutant triggers for arrhythmia, with various underlying mechanisms at play.10 These mechanisms include alterations in ion channels and currents, structural remodeling, calcium overload, inhibition of ionic pumps, and modulation of cardiac vagal control.Understanding the link between arrhythmia susceptibility after exposure to PM and the increasing incidence of sudden death globally11 presents a challenging research endeavor. Ethical constraints limit the feasibility of personalized exposure studies, calling for innovative approaches. One such promising avenue is the utilization of in vitro “on-a-chip” technology employing human-induced pluripotent stem cells derived from individuals with known exposure histories. By differentiating these cells into three-dimensional organoids,12 researchers may gain valuable insights into individual vulnerability and responses to air pollution–induced arrhythmia. Although this technology is still in its infancy (no papers about the effects of PM exposure on cardiac organoids have been presented in the literature yet), we firmly believe it has the potential to provide crucial insights, particularly for workers and others who are constantly exposed to high indoor and outdoor levels of pollutants.As scientific knowledge advances and innovative technologies continue to mature, there is hope for a future where the silent threat of air pollution on cardiac health is better understood and effectively mitigated for the well-being of humanity.AcknowledgmentsThis work was supported by the University of Parma through the action BANDO YIRG UNIPR, co-funded by MUR-Italian Ministry of Universities and Research - D.M. 737/2021 - Programma Nazionale per la Ricerca (PNR) - Piano Nazionale di Ripresa e Resilienza (PNRR) – NextGenerationEU and National Recovery and Resilience Plan (to M.M.).References1. Ji JS. 2022. 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Crossref, Medline, Google Scholar12. Bilinovich SM, Uhl KL, Lewis K, Soehnlen X, Williams M, Vogt D, et al.2020. Integrated RNA sequencing reveals epigenetic impacts of diesel particulate matter exposure in human cerebral organoids. Dev Neurosci 42(5–6):195–207, PMID: 33657557, 10.1159/000513536. Crossref, Medline, Google ScholarThe authors declare they have nothing to disclose.FiguresReferencesRelatedDetailsRelated articlesGlobal Air Pollutant Phenanthrene and Arrhythmic Outcomes in a Mouse Model1 November 2023Environmental Health Perspectives Vol. 131, No. 11 November 2023Metrics About Article Metrics Publication History Manuscript received31 July 2023Manuscript revised8 September 2023Manuscript accepted25 September 2023Originally published1 November 2023 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. 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