Polycyclic aromatic hydrocarbons induce endothelial injury through miR‐155 to promote atherosclerosis

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are considered as an external factor that induces atherosclerotic cardiovascular disease. Although miR‐155 is known to be involved in cardiovascular disease, whether it is involved in PAH‐induced arteriosclerosis remains unclear. We evaluated the effects of PAHs on vascularization, permeability, and miR‐155 expression in HUVECs. We found that PAHs‐induced sclerosis of HUVECs was characterized by increasing permeability, decreasing proliferation, and vascular lumen number. The expression of miR‐155 was upregulated by PAHs treatment, and transfection with miR‐155 inhibitor could reverse above effect of PAHs‐induced sclerosis. Meanwhile, transcriptome sequencing revealed that 63 genes were downregulated in the group of PAHs treatment alone, and were then upregulated in the miR‐155 inhibitor group. These genes were mainly involved in complement and coagulation cascades, cytokine‐cytokine receptor interaction, TNF signaling pathway, and NF‐kappa B signaling pathway. Among these 63 genes, SERPIND1 was directly targeted and regulated by miR‐155. Further in vivo experiments in ApoE−/− mice confirmed that PAH accelerates the development of arteriosclerosis by promoting the expression of miR‐155 to downregulate the SERPIND1. Therefore, PAH exaggerates atherosclerosis by activating miR‐155‐dependent endothelial injury. This study provides a fundamental insight on the miR‐155 mechanism for PAHs enhancing atherosclerosis and miR‐155 potentially serving as a novel drug target.

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“…Inhalation of these materials induces local and systemic changes in the immune system which may impair critical cell defense mechanisms …..Our results demonstrated that exposure to PAHs leads to cell activation and deteriorates mitochondrial function of the macrophage thus facilitating growth of M. tuberculosis ." Sada-Ovalle et al (2018) respiratory tract; immune system; cell defense mechanisms; immune cells; macrophages; Mycobacterium tuberculosis ; THP-1; monocyte-derived macrophages; cell activation; mitochondrial function IIC “Polycyclic aromatic hydrocarbons induce endothelial injury through miR-155 to promote atherosclerosis" He et al (2021) atherosclerotic cardiovascular disease; miR-155; vascularization; permeability; miR-155 expression in HUVECs; permeability; proliferation; vascular lumen number; transcriptome sequencing; 63 genes; complement cascades; coagulation cascades; cytokine-cytokine receptor interaction; TNF signaling pathway; NF-kappa B signaling pathway; SERPIND1 DNS “this study suggests that exposure to PAHs leads to cortical thinning in the elderly in the absence of known neurological diseases. The affected brain regions included frontal, parietal, temporal, and insular lobes.…”