Polycyclic Aromatic Hydrocarbons (PAHs) Exposure Triggers Inflammation and Endothelial Dysfunction in BALB/c Mice: A Pilot Study

Abstract

The particulate matter present in air pollution is a complex mixture of solid and liquid particles that vary in size, origin, and composition, among which are polycyclic aromatic hydrocarbons (PAHs). Although exposure to PAHs has become an important risk factor for cardiovascular disease, the mechanisms by which these compounds contribute to increased cardiovascular risk have not been fully explored. The aim of the present study was to evaluate the effects of PAH exposure on systemic pro-inflammatory cytokines and markers of endothelial dysfunction. An intervention was designed using a murine model composed of twenty BALB/c male mice separated into controls and three groups exposed to a mixture of phenanthrene, fluoranthene, and pyrene using three different concentrations. The serum levels of the inflammatory cytokines and gene expression of adhesion molecules located on endothelial cells along with inflammatory markers related to PAH exposure in aortic tissue were determined. Furthermore, the expression of the ICAM-1 and VCAM-1 proteins was evaluated. The data showed significant differences in IL-6 and IFN-γ in the serum. In the gene expression, significant differences for ICAM-1, VCAM-1, and E-Selectin were observed. The results suggest that phenanthrene, fluoranthene, and pyrene, present in air pollution, stimulate the increase in serum inflammatory cytokines and the expression of markers of endothelial dysfunction in the murine model studied, both relevant characteristics associated with the onset of disease atherosclerosis and cardiovascular disease.

Impact of Wildfires on Cardiovascular Health

“…In a preclinical study, Rojas et al 163 noted that a single exposure to a mixture of PAHs similar to those found in WFS significantly elevated plasma concentration of IL-6, IL-1β, TNF-α, and IFN-γ in male BALB/c mice. Analysis of aortic tissues further revealed transcriptomic upregulation of genes associated with endothelial dysfunction ( Vcam1 , Icam1 , and Sele ) and reduction-oxidation imbalance, consistent with the accumulation of adhesion molecules ICAM-1 and VCAM-1.…”

“…Analysis of aortic tissues further revealed transcriptomic upregulation of genes associated with endothelial dysfunction ( Vcam1 , Icam1 , and Sele ) and reduction-oxidation imbalance, consistent with the accumulation of adhesion molecules ICAM-1 and VCAM-1. 163 Finally, Robertson et al 164 reported that a single, 4-hour-long O 3 exposure at 1 ppm concentration promoted lung inflammation and attenuated the acetylcholine-mediated vasodilatation of isolated aortas from female C57BL/6 but not CD36 −/− mice, compared with filtered air. The latter, however, was recapitulated in naïve isolated aortas from female C57BL/6 mice following treatment with serum from O 3 -exposed mice of both genotypes.…”

Association of Endocrine-Disrupting Chemicals with All-Cause and Cause-Specific Mortality in the U.S.: A Prospective Cohort Study

“…The cardiovascular toxicity of PAHs was validated by several studies based on experiment. Studies determined that PAH exposure on mice and humans could cause oxidative, inflammation, lipid dysfunction, and endothelial dysfunction, which were linked to higher systolic blood pressure and heart rate variability. − Despite these, evidence displayed that an epigenetic factor such as DNA methylation could be disturbed by PAHs exposure and dysregulate the downstream gene expression, which may also help explain the complex effects on PAHs exposure on cardiovascular disease …”

Influence of Exposure Pathways on Tissue Distribution and Health Impact of Polycyclic Aromatic Hydrocarbon Derivatives

“…A study of nasal drops of PAHs in BALB/ c mice found that PAHs such as phenanthrene, fluoranthene, and pyrene caused inflammation and endothelial dysfunction in the mice. 154 Endothelial dysfunction is an important cause of several cardiovascular diseases, including atherosclerosis. Some in vitro studies have shown that PAHs, NPAHs, and OPAHs can cause endothelial dysfunction.…”

“…Toxicological studies reached the same conclusion. A study of nasal drops of PAHs in BALB/c mice found that PAHs such as phenanthrene, fluoranthene, and pyrene caused inflammation and endothelial dysfunction in the mice . Endothelial dysfunction is an important cause of several cardiovascular diseases, including atherosclerosis.…”