Polycyclic aromatic hydrocarbons induce endothelial injury through miR-155 to promote atherosclerosis.
Xiao-Nan HeJin-Yuan XinJin-Liang ZhanFang-Kun WuJian HouZhao-Bin SunJi WangXiao-Ling ZhangYing-Chen BaiPublished in: Environmental and molecular mutagenesis (2021)
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.
Keyphrases
- polycyclic aromatic hydrocarbons
- cell proliferation
- long non coding rna
- long noncoding rna
- cardiovascular disease
- signaling pathway
- poor prognosis
- heavy metals
- type diabetes
- single cell
- rheumatoid arthritis
- gene expression
- drug delivery
- emergency department
- genome wide
- epithelial mesenchymal transition
- human health
- insulin resistance
- adipose tissue
- diabetic rats
- toll like receptor
- mild cognitive impairment
- combination therapy
- ultrasound guided
- genome wide identification