miRNA 146b-5p Protects Against Atherosclerosis by Inhibiting Vascular Smooth Muscle Cell Proliferation and Migration

Abstract

Aim: To explore the potentially important role of miRNA 146b-5p (miR-146b) during the development of atherosclerosis. Materials & methods: Proliferation, migration and luciferase assays and mouse models were used to determine the functions of miR-146b. Results: miR-146b was identified as substantially upregulated in the aortic plaques of ApoE-/- mice as well as in response to inflammatory cytokines. Overexpression of miR-146b repressed proliferation and migration of vascular smooth muscle cells by downregulating Bag1 and Mmp16, respectively. Adeno-associated virus-mediated miR-146b overexpression inhibited neointima formation after carotid injury and suppressed atherosclerotic plaque formation in Western diet-induced ApoE-/- mice. Conclusion: miR-146b is a novel regulator of vascular smooth muscle cell function induced by inflammatory response, specifically in neointima formation, and offers a novel therapeutic strategy for treating atherosclerosis.

Keywords::

• atherosclerosis
• epigenetics
• inflammation
• migration
• miR-146b
• neointima formation
• proliferation
• vascular smooth muscle cells

Financial&competing interests disclosure

This study was funded by the research grants National Nature Science Foundation of China (no. 81370417) and Hubei Natural Science Foundation Project (no. 2018CFB465). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance (English language and spelling check) was utilized in the production of this manuscript and founded by National Nature Science Foundation of China (no. 81370417) and Hubei Natural Science Foundation Project (no. 2018CFB465).

Ethical conduct of research

Sun D, Xiang G, Wang J et al. state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Additional information

Funding

This study was funded by the research grants National Nature Science Foundation of China (no. 81370417) and Hubei Natural Science Foundation Project (no. 2018CFB465). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance (English language and spelling check) was utilized in the production of this manuscript and founded by National Nature Science Foundation of China (no. 81370417) and Hubei Natural Science Foundation Project (no. 2018CFB465).