Evaluation of Early Biomarkers of Atherosclerosis Associated with Polychlorinated Biphenyl Exposure: An and Study.

BACKGROUND

Miscellaneous cardiovascular risk factors have been defined, but the contribution of environmental pollutants exposure on cardiovascular disease (CVD) remains underappreciated.

OBJECTIVE

We investigated the potential impact of typical environmental pollutant exposure on atherogenesis and its underlying mechanisms.

METHODS

We used human umbilical vein endothelial cells (HUVECs) and apolipoprotein E knockout () mice to investigate how 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ, a toxic polychlorinated biphenyl metabolite) affects atherogenesis and identified early biomarkers of CVD associated with PCB29-pQ exposures. Then, we used long noncoding RNAs (lncRNAs) -overexpressing mice and apolipoprotein E/caveolin 1 double-knockout () mice to address the role of these early biomarkers in PCB29-pQ-induced atherogenesis. Plasma samples from patients with coronary heart disease (CHD) were also used to confirm our findings.

RESULTS

Our data indicate that lncRNA bound to via argonaute 2 in PCB29-pQ-challenged HUVECs. Our mRNA sequencing assay identified transforming growth () as a possible target gene of ; sponged and inhibited the binding of to . The effect of PCB29-pQ-induced endothelial injury, vascular inflammation, development of plaques, and atherogenesis in mice was greater with -mediated inhibition, whereas -overexpressing mice and mice showed the opposite effect. Consistently, plasma levels of and were found to be significantly associated individuals diagnosed with CHD.

DISCUSSIONS

These findings demonstrated that a mechanism-based, integrated-omics approach enabled the identification of potentially clinically relevant diagnostic indicators and therapeutic targets of CHD mediated by environmental contaminants using and models of HUVECs and and mice. https://doi.org/10.1289/EHP9833.