Elevated plasma solMER concentrations link ambient PM2.5 and PAHs to myocardial injury and reduced left ventricular systolic function in children

Zihan Chen; Xia Huo; Yu Huang; Zhiheng Cheng; Xijin Xu; Zhi Li

doi:10.1016/j.envpol.2024.124151

Elevated plasma solMER concentrations link ambient PM_2.5 and PAHs to myocardial injury and reduced left ventricular systolic function in children

Environ Pollut. 2024 May 11:124151. doi: 10.1016/j.envpol.2024.124151. Online ahead of print.

Authors

Zihan Chen¹, Xia Huo², Yu Huang³, Zhiheng Cheng⁴, Xijin Xu⁵, Zhi Li⁶

Affiliations

¹ Department of Cardiology, the First Affiliated Hospital of Shantou University Medical College, Shantou 515000, Guangdong, China; Shantou University Medical College, Shantou 515041, Guangdong, China.
² Laboratory of Environmental Medicine and Developmental Toxicology, Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou 511443, Guangdong, China.
³ Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041, Guangdong, China.
⁴ Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands.
⁵ Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, Guangdong, China.
⁶ Department of Cardiology, the First Affiliated Hospital of Shantou University Medical College, Shantou 515000, Guangdong, China. Electronic address: lizhi519@126.com.

PMID: 38740242
DOI: 10.1016/j.envpol.2024.124151

Abstract

Exposure to fine particulate matter (PM_2.5) and polycyclic aromatic hydrocarbons (PAHs) is known to be associated with the polarization of pro-inflammatory macrophages and the development of various cardiovascular diseases. The pro-inflammatory polarization of resident cardiac macrophages (cMacs) enhances the cleavage of membrane-bound myeloid-epithelial-reproductive receptor tyrosine kinase (MerTK) and promotes the formation of soluble MerTK (solMER). This process influences the involvement of cMacs in cardiac repair, thus leading to an imbalance in cardiac homeostasis, myocardial injury, and reduced cardiac function. However, the relative impacts of PM_2.5 and PAHs on human cMacs have yet to be elucidated. In this study, we aimed to investigate the effects of PM_2.5 and PAH exposure on solMER in terms of myocardial injury and left ventricular (LV) systolic function in healthy children. A total of 258 children (aged three to six years) were recruited from Guiyu (an area exposed to e-waste) and Haojiang (a reference area). Mean daily PM_2.5 concentration data were collected to calculate the individual chronic daily intake (CDI) of PM_2.5. We determined concentrations of solMER and creatine kinase MB (CKMB) in plasma, and hydroxylated PAHs (OH-PAHs) in urine. LV systolic function was evaluated by stroke volume (SV). Higher CDI values and OH-PAH concentrations were detected in the exposed group. Plasma solMER and CKMB were higher in the exposed group and were associated with a reduced SV. Elevated CDI and 1-hydroxynaphthalene (1-OHNa) were associated with a higher solMER. Furthermore, increased solMER concentrations were associated with a lower SV and higher CKMB. CDI and 1-OHNa were positively associated with CKMB and mediated by solMER. In conclusion, exposure to PM_2.5 and PAHs may lead to the pro-inflammatory polarization of cMacs and increase the risk of myocardial injury and systolic function impairment in children. Furthermore, the pro-inflammatory polarization of cMacs may mediate cardiotoxicity caused by PM_2.5 and PAHs.

Keywords: Cardiotoxicity; Fine particulate matter; MerTK; Polycyclic aromatic hydrocarbons; Resident cardiac macrophages.