Evaluation of Early Biomarkers of Atherosclerosis Associated with Polychlorinated Biphenyl Exposure: An in Vitro and in Vivo Study

Abstract

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) HDAC7-AS1 –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 HDAC7-AS1 bound to MIR-7-5p via argonaute 2 in PCB29-pQ–challenged HUVECs. Our mRNA sequencing assay identified transforming growth ( ) as a possible target gene of MIR-7-5p ; HDAC7-AS1 sponged MIR-7-5p and inhibited the binding of to MIR-7-5p . The effect of PCB29-pQ–induced endothelial injury, vascular inflammation, development of plaques, and atherogenesis in mice was greater with MIR-7-5p –mediated inhibition, whereas HDAC7-AS1 –overexpressing mice and 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 and mice. https://doi.org/10.1289/EHP9833

Angiogenic Activity and Mechanism for Bisphenols on Endothelial Cell and Mouse: Evidence of a Structural-Selective Effect

“…CVDs remain the leading cause of death and disability globally, and the risk factor characterization including environmental pollution deserved an urgent investigation . As one of the most widely used chemical compounds in daily consumer products, synthetic bisphenols have traditionally been recognized as an environmental health risk factor mainly as typical EDCs with steroid hormonal effects. − Epidemiological and animal data support the potential involvement of bisphenol exposure as for disrupting arterial health and developing CVD risk in humans. , Recent research suggested that the maternal bisphenol exposure level might influence fetal vascular development .…”

Caveolin-1 in endothelial cells: A potential therapeutic target for atherosclerosis

“…In line with this, Cav1 deficiency has been shown to reduce AS and plaque inflammation by reducing leukocyte influx and systemic anti-inflammatory T lymphocytes [ 125 ]. In AS induced by PCB29-PQ (a metabolite of the typical environmental pollutant PCB), Cav1 can act as a scaffold for inflammatory signaling by negatively regulating TGF-β and Cav1 phosphorylation to activate pro-inflammatory ROS [ 127 ]. Cav1 activates cellular inflammatory states through various signaling pathways.…”