Elsevier

Journal of Hazardous Materials

Volume 418, 15 September 2021, 126261
Journal of Hazardous Materials

Research Paper
Combustion-derived particulate organic matter associated with hemodynamic abnormality and metabolic dysfunction in healthy adults

https://doi.org/10.1016/j.jhazmat.2021.126261Get rights and content

Highlights

  • POM including 18 PAHs and 25 n-alkanes was measured in the present study.

  • Exposure to POM could significantly prompt the genesis of hemodynamic abnormality.

  • POM was also associated with heightened insulin resistance and calcific responses.

  • Stronger effects were observed for POM from traffic emissions and coal burning.

Abstract

Epidemiological evidence on cardiometabolic health of particulate organic matter (POM) and its sources is sparse. In a panel of 73 healthy adults in Beijing, China, daily concentrations of ambient fine particulate matter-bound polycyclic aromatic hydrocarbons (PAHs) and n-alkanes were measured throughout the study period, and Positive Matrix Factorization approach was used to identity PAHs sources. Linear mixed-effect models and mediation analyses were applied to examine the associations and potential interlink pathways between POM and biomarkers indicative of hemodynamics, insulin resistance, vascular calcification and immune inflammation. We found that significant alterations in cardiometabolic measures were associated with POM exposures. In specific, interquartile range increases in PAHs concentrations at prior up to 9 days were observed in association with significant elevations of 2.6–2.9% in diastolic blood pressure, 6.6–8.1% in soluble ST2, 10.5–14.5% in insulin, 40.9–45.7% in osteoprotegerin, and 36.3–48.7% in interleukin-17A. Greater associations were generally observed for PAHs originating from traffic emissions and coal burning. Mediation analyses revealed that POM exposures may prompt the genesis of hemodynamic abnormalities, possibly via worsening insulin resistance and calcification potential. These findings suggested that cardiometabolic health benefits would be achieved by reducing PM from combustion emissions.

Introduction

Ambient particulate matter (PM) with an aerodynamic diameter smaller than 2.5 µm (PM2.5) is a complex mixture of chemicals originating from a variety of sources that has been widely recognized as an important contributor to premature deaths worldwide, with the largest portion attributable to cardiovascular mortality (Cohen et al., 2017). Ambient PM in most urban areas is primarily generated from fossil fuel combustions with strong impacts on an array of cardiometabolic disorders, including atherosclerosis, diabetes and hemodynamic abnormalities (e.g., prohypertensive action) (Al-Kindi et al., 2020). Growing evidence supports that the toxic property of PM may largely depend on its heterogeneous components and sources, and combustion-derived carbonaceous fractions of PM2.5 (e.g., particulate organic matter [POM]) can be more responsible for detrimental health effects posed by PM mixtures (Rohr and Wyzga, 2012). Indeed, POM has been shown to be independently associated with occurrence of cardiometabolic diseases, and the risk burden can be significantly mitigated by reducing POM exposures (Keebaugh et al., 2015, Lin et al., 2019).

The prevailing hypothesis is that inhaled POM is capable of translocation across alveolar epithelium into circulation and accumulation at sites of vasculature and adipose tissues, thus might exert adverse effects on metabolic and hemodynamic homeostasis (Holme et al., 2019). Emerging evidence suggests that metabolic dysfunction caused by combustion-related air pollutants may worsen the atherosclerotic progression, thereby leading to hemodynamic abnormalities and future cardiometabolic events eventually (Brook et al., 2017, Haberzettl et al., 2016, Johnson et al., 2020, O'Neill et al., 2005). Vascular calcification, a disorder that heightens plaque burden and blood vessel hardening, is one of the most prominent clinical manifestations of cardiometabolic diseases in vulnerable individuals (Chen et al., 2020). Mechanistically, studies have shown that insulin resistance-related metabolic changes play a role in calcification processes via activations of the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) system and bone morphogenetic proteins (BMPs) (Harper et al., 2016). Disruptions of biological activities of RANKL, OPG, and BMPs are likely to induce osteoblast-like differentiation of smooth muscle cells (VSMCs), alter mineral metabolism and arterial elasticity, heighten calcification potential, and prompt hemodynamic abnormalities (e.g., hypertension and chronic heart failure) (Collin-Osdoby, 2004). Lower expressions of RANKL, OPG and BMPs in macrophages, T cells, endothelial cells and VSMCs can be upregulated in the presence of cardiometabolic stimuli, such as adiponectin and inflammatory cytokines (Collin-Osdoby, 2004, Ono et al., 2020). Further, infiltration of immune cells into adipose tissues can result in secretions of adipokines, growth factors and cytokines, eventually heightening insulin resistance and calcification process. Compelling evidence also suggests that POM can be a trigger of immune-inflammatory responses (Brook et al., 2017).

Recent studies showed that inflammation provoked by organic components of diesel exhaust particles in human endothelial cells and macrophages were significantly inhibited by the aryl hydrocarbon receptor (AHR) antagonist, indicating that the proinflammatory effects might be mediated via activation of the AHR pathway (Vogel et al., 2020). The AHR, an environment-sensing transcription factor that plays important roles in blood pressure (BP) regulation, insulin resistance, calcifying action, and atherosclerosis, can be activated by various pollutants including polycyclic aromatic hydrocarbons (PAHs) (Kim et al., 2020, Zhu et al., 2019). PAHs mixtures bound to PM2.5, which usually account for 90% of total PAHs in urban ambient air, largely originate from combustion process, such as traffic, coal burning and industrial activities (Kong et al., 2010). Limited epidemiological studies indicated that environmental PAHs exposures were associated with elevated brachial BP and insulin resistance (Choi et al., 2015, Jacobs et al., 2012), and mechanistic evidence supports that insulin resistance attributable to concentrated ambient PM2.5 could worsen the functioning of vascular system (Haberzettl et al., 2016). Exposure to PAH-rich particles in vivo also reported that PAHs could be retained in lipid droplets in various organs for at least 8 days, and the adverse responses provoked by PAHs may persist over longer time even after exposure removed (Bui et al., 2012). Nevertheless, no human study has ever assessed whether metabolic changes attributable to combustion-derived POM, including increased insulin resistance and calcific responses, may prompt the genesis of hemodynamic abnormalities in a manner potentially predisposing to the onset of clinically overt cardiometabolic events.

Resulting from rapid urbanization and economic development in recent decades, China has large emission of PAHs of 106 Gg annually, which accounts for nearly 21% of the total emission of PAHs around the world (Shen et al., 2013). The concentration distribution of ambient particulate-bound PAHs in China is also highly varied across regions with annual averages ranging from 3 to 910 ng/m3, and higher levels often observed in the cold months (Han et al., 2019, Yan et al., 2019). We have previously shown that exposure to PM2.5 is associated with elevations in BP and systemic inflammation during the 2008 Beijing Olympics with unprecedented pollution control measures on traffic and industrial emission reductions (Rich et al., 2012). Further, we observed greater elevations of brachial BP in relation to ambient PM2.5 in the Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunction in Healthy Adults) among participants who were overweight, suggesting that metabolic conditions may regulate PM-induced hemodynamic changes (Huang et al., 2018). Here, in the extended analysis of AIRCHD study, we hypothesized that exposure to POM could alter hemodynamics via worsening insulin resistance and vascular calcification process. We aimed to investigate the impacts and potential interlink pathways of ambient PM2.5-bound major organic components exposures, focusing on PAHs and n-alkanes, on a suite of biomarkers indicative of hemodynamics, insulin resistance, vascular calcification and immune inflammation. We further apportioned the sources of PM2.5-bound PAHs and discerned the emission sources most responsible for the biological changes.

Section snippets

Study participants and design

The protocol of the Beijing AIRCHD study has been described in details previously (Xu et al., 2019). The study sample size was determined to be 60 participants using a significance level (type I error) at 0.05 with an 80% statistical power and a 10% rate of loss to follow-up based on our previous study (Rich et al., 2012). In the current analysis, 73 non-smoking healthy adults participated in the baseline examination and four repeated clinical visits between November 2014 and January 2016. At

Results

Descriptive statistics of the study participants are summarized in Table 1, with mean (SD) age of 23.3 (5.4) years. Urinary cotinine levels were measured with a mean level of 20.8 ng/mg Cr and a median level of 2.6 ng/mg Cr, indicating low impacts of potential environmental tobacco smoke exposure in this study population. As shown in Fig. 1, we found large day-to-day variations in ambient POM concentrations over the study period. For instance, daily average concentrations varied from 2.7 to

Discussion

We have shown here that short-term exposure to ambient PM2.5-bound PAHs and n-alkanes, indicators of POM mainly from the process of fossil fuel combustion, is associated with significant elevations in BP and sST2 levels. Higher concentrations of POM exposures were also related to heightening insulin resistance, vascular calcification, and immune inflammation (including elevated levels of lymphocyte and monocyte /macrophage activation biomarkers). Importantly, mediation analyses revealed that

CRediT authorship contribution statement

Hongbing Xu: Conceptualization, Data curation, Methodology, Formal analysis, Visualization, Writing - original draft. Yutong Zhu: Conceptualization, Data curation, Methodology, Formal analysis, Visualization, Writing - original draft. Lijuan Li: Conceptualization, Data curation, Methodology, Formal analysis, Visualization, Writing - original draft. Shengcong Liu: Data curation, Methodology. Xiaoming Song: Data curation, Methodology. Tieci Yi: Data curation, Methodology. Yang Wang: Data

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

We would like to thank all study participants. This work was supported by China National Key Research and Development Projects, China (2017YFC0211701), National Natural Science Foundation of China, China (81773381), and Michigan Medicine-PKUHSC Joint Institute for Translational and Clinical Research, China and USA (2013-3-02).

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