Evaluation of Early Biomarkers of Atherosclerosis Associated with Polychlorinated Biphenyl Exposure: An in Vitro and in Vivo 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 ([Formula: see text]) 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) HDAC7-AS1–overexpressing [Formula: see text] mice and apolipoprotein E/caveolin 1 double-knockout ([Formula: see text]) 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 HDAC7-AS1 bound to MIR-7-5p via argonaute 2 in PCB29-pQ–challenged HUVECs. Our mRNA sequencing assay identified transforming growth [Formula: see text] ([Formula: see text]) as a possible target gene of MIR-7-5p; HDAC7-AS1 sponged MIR-7-5p and inhibited the binding of [Formula: see text] to MIR-7-5p. The effect of PCB29-pQ–induced endothelial injury, vascular inflammation, development of plaques, and atherogenesis in [Formula: see text] mice was greater with MIR-7-5p–mediated [Formula: see text] inhibition, whereas HDAC7-AS1–overexpressing [Formula: see text] mice and [Formula: see text] mice showed the opposite effect. Consistently, plasma levels of HDAC7-AS1 and MIR-7-5p 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 in vitro and in vivo models of HUVECs and [Formula: see text] and [Formula: see text] mice. https://doi.org/10.1289/EHP9833