MicroRNA-22 inhibition promotes the development of atherosclerosis via targeting interferon regulator factor 5.

Abstract

Atherosclerosis is generally accepted as a chronic inflammatory disease and is the most important pathological process underlying the cardiovascular diseases. MiR-22 exerts an important role in tumorgenesis, obesity and NAFLD development, as well as cardiovascular diseases. However, a certain role of miR-22 in the pathogenesis of atherosclerosis remains undetermined. Here, we showed that miR-22 exhibited a negative association with the deteriorated atherosclerotic plaque and showed significant downregulated expression in macrophages. Next, treatment of ApoE deficiency (ApoE-/-) mice with miR-22 inhibitors which were then subjected to high fat diet (HFD) for 12 weeks were performed to investigate the function of miR-22 on atherogenesis. The results exhibited that miR-22 inhibition dramatically promoted atherosclerotic plaques but attenuated plaque stabilization which were accompanied by decreased smooth muscle cell and collagen content, but increased macrophage infiltration and lipid accumulation. More importantly, the in vivo and in vitro experiments suggested that miR-22 inhibition accelerated inflammatory response and foam cell formation. Mechanistically, we demonstrated interferon regulator factor 5 (IRF5) was an important target of miR-22 and it was required for the regulation of inflammation mediated by miR-22 inhibition. Collectively, these evidences revealed that miR-22 inhibition promoted the atherosclerosis progression through activation of IRF5.

• Authors: Zhenhua Wu, Jie Geng, Yunpeng Bai, Yujuan Qi, Chao Chang, Yan Jiao, Zhigang Guo
• Journal: Experimental cell research (Exp Cell Res) Vol. 409 Issue 2 Pg. 112922 (12 15 2021) ISSN: 1090-2422 [Electronic] United States
• PMID: 34780785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Interferon Regulatory Factors
• Irf5 protein, mouse
• MicroRNAs
• Mirn22 microRNA, mouse

Topics

• Animals
• Apoptosis
• Atherosclerosis (etiology, metabolism, pathology)
• Cell Proliferation
• Cells, Cultured
• Diet, High-Fat
• Foam Cells (immunology)
• Gene Expression Regulation
• Inflammation (etiology, metabolism, pathology)
• Interferon Regulatory Factors (genetics, metabolism)
• Mice
• Mice, Knockout, ApoE
• MicroRNAs (antagonists & inhibitors, genetics)
• Plaque, Atherosclerotic (etiology, metabolism, pathology)