Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways.

Manman Wang, Jiao Li, Jiageng Cai, Lijun Cheng, Xuewen Wang, Pengjuan Xu, Guangping Li, Xue Liang

BioMed research international 2020

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Our previous study demonstrated that the expression of miR-16 was downregulated in the cell and animal models of atherosclerosis (AS), a main contributor to coronary artery disease (CAD). Overexpression of miR-16 inhibited the formation of foam cells by exerting anti-inflammatory roles. These findings indicated miR-16 may be an anti-atherogenic and CAD miRNA. The goal of this study was to further validate the expression of miR-16 in CAD patients and explore its therapeutic roles in an AS animal model. A total of 40 CAD patients and 40 non-CAD people were prospectively registered in our study. The AS model was established in ApoE-/- mice fed a high-fat diet. The model mice were randomly treated with miR-16 agomiR (n = 10) or miR-negative control (n = 10). Hematoxylin-eosin staining was conducted for histopathological examination in thoracic aorta samples. ELISA and immunohistochemistry were performed to determine the expression levels of inflammatory factors (IL-6, TNF-α, MCP-1, IL-1β, IL-10, and TGF-β). qRT-PCR and western blotting were carried out to detect the mRNA and protein expression levels of PDCD4, miR-16, and mitogen-activated protein kinase pathway-related genes. Compared with the normal control, miR-16 was downregulated in the plasma and peripheral blood mononuclear cell of CAD patients, and its expression level was negatively associated with IL-6 and the severity of CAD evaluated by the Gensini score, but positively related with IL-10. Injection of miR-16 agomiR in ApoE-/- mice reduced the formation of atherosclerotic plaque and suppressed the accumulation of proinflammatory factors (IL-6, TNF-α, MCP-1, and IL-1β) in the plasma and tissues but promoted the secretion of anti-inflammatory factors (IL-10 and TGF-β). Mechanism analysis showed overexpression of miR-16 might downregulate target mRNA PDCD4 and then activate p38 and ERK1/2, but inactivate the JNK pathway. Our findings suggest miR-16 may be a potential diagnostic biomarker and therapeutic target for atherosclerotic CAD. Copyright © 2020 Manman Wang et al.

Citation

Manman Wang, Jiao Li, Jiageng Cai, Lijun Cheng, Xuewen Wang, Pengjuan Xu, Guangping Li, Xue Liang. Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways. BioMed research international. 2020;2020:8504238