Cargando…
Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways
BACKGROUND: 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....
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391121/ https://www.ncbi.nlm.nih.gov/pubmed/32775445 http://dx.doi.org/10.1155/2020/8504238 |
_version_ | 1783564583179386880 |
---|---|
author | Wang, Manman Li, Jiao Cai, Jiageng Cheng, Lijun Wang, Xuewen Xu, Pengjuan Li, Guangping Liang, Xue |
author_facet | Wang, Manman Li, Jiao Cai, Jiageng Cheng, Lijun Wang, Xuewen Xu, Pengjuan Li, Guangping Liang, Xue |
author_sort | Wang, Manman |
collection | PubMed |
description | BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our findings suggest miR-16 may be a potential diagnostic biomarker and therapeutic target for atherosclerotic CAD. |
format | Online Article Text |
id | pubmed-7391121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-73911212020-08-06 Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways Wang, Manman Li, Jiao Cai, Jiageng Cheng, Lijun Wang, Xuewen Xu, Pengjuan Li, Guangping Liang, Xue Biomed Res Int Research Article BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our findings suggest miR-16 may be a potential diagnostic biomarker and therapeutic target for atherosclerotic CAD. Hindawi 2020-07-21 /pmc/articles/PMC7391121/ /pubmed/32775445 http://dx.doi.org/10.1155/2020/8504238 Text en Copyright © 2020 Manman Wang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Wang, Manman Li, Jiao Cai, Jiageng Cheng, Lijun Wang, Xuewen Xu, Pengjuan Li, Guangping Liang, Xue Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways |
title | Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways |
title_full | Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways |
title_fullStr | Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways |
title_full_unstemmed | Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways |
title_short | Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways |
title_sort | overexpression of microrna-16 alleviates atherosclerosis by inhibition of inflammatory pathways |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391121/ https://www.ncbi.nlm.nih.gov/pubmed/32775445 http://dx.doi.org/10.1155/2020/8504238 |
work_keys_str_mv | AT wangmanman overexpressionofmicrorna16alleviatesatherosclerosisbyinhibitionofinflammatorypathways AT lijiao overexpressionofmicrorna16alleviatesatherosclerosisbyinhibitionofinflammatorypathways AT caijiageng overexpressionofmicrorna16alleviatesatherosclerosisbyinhibitionofinflammatorypathways AT chenglijun overexpressionofmicrorna16alleviatesatherosclerosisbyinhibitionofinflammatorypathways AT wangxuewen overexpressionofmicrorna16alleviatesatherosclerosisbyinhibitionofinflammatorypathways AT xupengjuan overexpressionofmicrorna16alleviatesatherosclerosisbyinhibitionofinflammatorypathways AT liguangping overexpressionofmicrorna16alleviatesatherosclerosisbyinhibitionofinflammatorypathways AT liangxue overexpressionofmicrorna16alleviatesatherosclerosisbyinhibitionofinflammatorypathways |