Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2024 Dec;24(12):1348-1363.
doi: 10.1007/s12012-024-09931-9. Epub 2024 Oct 14.

Proteomics Reveals Divergent Cardiac Inflammatory and Metabolic Responses After Inhalation of Ambient Particulate Matter With or Without Ozone

Yue Ge  1 , Maliha S Nash  2 , Witold M Winnik  2 , Maribel Bruno  3 , William T Padgett  2 , Rachel D Grindstaff  2 , Mehdi S Hazari  2 , Aimen K Farraj  2
Affiliations
Comparative Study

Proteomics Reveals Divergent Cardiac Inflammatory and Metabolic Responses After Inhalation of Ambient Particulate Matter With or Without Ozone

Yue Ge et al. Cardiovasc Toxicol. 2024 Dec.

Abstract

Inhalation of ambient particulate matter (PM) and ozone (O3) has been associated with increased cardiovascular morbidity and mortality. However, the interactive effects of PM and O3 on cardiac dysfunction and disease have not been thoroughly examined, especially at a proteomic level. The purpose of this study was to identify and compare proteome changes in spontaneously hypertensive (SH) rats co-exposed to concentrated ambient particulates (CAPs) and O3, with a focus on investigating inflammatory and metabolic pathways, which are the two major ones implicated in the pathophysiology of cardiac dysfunction. For this, we measured and compared changes in expression status of 9 critical pro- and anti-inflammatory cytokines using multiplexed ELISA and 450 metabolic proteins involved in ATP production, oxidative phosphorylation, cytoskeletal organization, and stress response using two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) in cardiac tissue of SH rats exposed to CAPs alone, O3 alone, and CAPs + O3. Proteomic expression profiling revealed that CAPs alone, O3 alone, and CAPs + O3 differentially altered protein expression patterns, and utilized divergent mechanisms to affect inflammatory and metabolic pathways and responses. Ingenuity Pathway Analysis (IPA) of the proteomic data demonstrated that the metabolic protein network centered by gap junction alpha-1 protein (GJA 1) was interconnected with the inflammatory cytokine network centered by nuclear factor kappa beta (NF-kB) potentially suggesting inflammation-induced alterations in metabolic pathways, or vice versa, collectively contributing to the development of cardiac dysfunction in response to CAPs and O3 exposure. These findings may enhance understanding of the pathophysiology of cardiac dysfunction induced by air pollution and provide testable hypotheses regarding mechanisms of action.

Keywords: Cardiac dysfunction; Inflammation; Metabolism; Ozone (O3); Particulate matter (PM); Proteomics.

PubMed Disclaimer

Conflict of interest statement

Declarations Conflict of interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethical Approval This manuscript has been reviewed by The Center for Computational Toxicology and Exposure, United States Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

References

    1. Brook, R. D., Rajagopalan, S., Pope, C. A., Brook, J. R., Bhatnagar, A., et al. (2010). Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation, 121, 2331–2378. https://doi.org/10.1161/CIR.0b013e3181dbece1 - DOI - PubMed
    1. Posadas-Sánchez, R., Vargas-Alarcón, G., Cardenas, A., Texcalac-Sangrador, J. L., Citlalli Osorio-Yáñez, C., & Sanchez-Guerra, M. (2022). Long-term exposure to ozone and fine particulate matter and risk of premature coronary artery disease: Results from genetics of atherosclerotic disease Mexican study. Biology, 11, 1122–1136. - DOI - PubMed - PMC
    1. Liu, C., Chen, R., Sera, F., Vicedo-Cabrera, A. M., Guo, Y., Tong, S., Lavigne, E., Correa, P. M., Ortega, N. V., et al. (2023). Interactive effects of ambient fine particulate matter and ozone on daily mortality in 372 cities: Two stage time series analysis. BMJ, 383, e075203. https://doi.org/10.1136/bmj-2023-075203 - DOI - PubMed - PMC
    1. Fakhri, A. A., Ilic, L. M., Wellenius, G. A., Urch, B., Silverman, F., Gold, D. R., & Mittleman, M. A. (2009). Autonomic effects of controlled fine particulate exposure in young healthy adults: Effect modification by ozone. Environmental Health Perspectives, 117, 1287–1292. https://doi.org/10.1289/ehp.0900541 - DOI - PubMed - PMC
    1. Sivagangabalan, G., Spears, D., Masse, S., Urch, B., Brook, R. D., Silverman, F., Gold, D. R., et al. (2011). The effect of air pollution on spatial dispersion of myocardial repolarization in healthy human volunteers. Journal of the American College of Cardiology, 57, 198–206. https://doi.org/10.1016/j.jacc.2010.08.625 - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources