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Polycyclic aromatic hydrocarbons induce endothelial injury through miR‐155 to promote atherosclerosis
Author(s) -
He XiaoNan,
Xin JinYuan,
Zhan JinLiang,
Wu FangKun,
Hou Jian,
Sun ZhaoBin,
Wang Ji,
Zhang XiaoLing,
Bai YingChen
Publication year - 2021
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.22454
Subject(s) - downregulation and upregulation , arteriosclerosis , transcriptome , inflammation , cytokine , mir 155 , signal transduction , chemistry , cancer research , microbiology and biotechnology , pharmacology , gene expression , biology , gene , immunology , endocrinology , biochemistry
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.