miR-221 Alleviates the Ox-LDL-Induced Macrophage Inflammatory Response via the Inhibition of DNMT3b-Mediated NCoR Promoter Methylation

الملخص EN

Atherosclerosis (AS) is a chronic inflammatory disease, and macrophages play a key role in all phases of AS.

Recent studies have shown that miR-221 is a biomarker for AS and stroke; however, the role and mechanism of miR-221 in AS are unclear.

Herein, we found that miR-221 and NCoR levels were decreased in ox-LDL-treated THP-1-derived macrophages.

In contrast, DNMT3b, IL-6, and TNF-α expression levels were increased under these conditions.

Upregulation of miR-221 or NCoR could partially inhibit ox-LDL-induced IL-6 and TNF-α expression.

Further studies showed that DNMT3b was a target of miR-221.

DNMT3b inhibition also suppressed IL-6 and TNF-α expression and increased NCoR expression in the presence of ox-LDL.

Moreover, DNMT3b was involved in ox-LDL-induced DNA methylation in the promoter region of NCoR.

These findings suggest that miR-221 suppresses ox-LDL-induced inflammatory responses via suppressing DNMT3b-mediated DNA methylation in the promoter region of NCoR.

These results provide a rationale for using intracellular miR-211 as a possible antiatherosclerotic target.