Blockade of 146b-5p promotes inflammation in atherosclerosis-associated foam cell formation by targeting TRAF6

Abstract

Atherosclerosis (AS) is a chronic inflammation in response to lipid accumulation. Increasing evidence has demonstrated that numerous microRNAs (miRs) have critical roles in inflammatory responses. A previous study suggested that miR-146b-5p is possibly associated with AS; however, its exact role has remained largely elusive. The present study aimed to investigate the potential role of miR-146b-5p in AS and to explore the underlying mechanism. Fist, the levels of miR-146b-5p were determined in foam cells and clinical specimens from patients with AS by reverse-transcription quantitative PCR. The role of miR-146b-5p in AS was then investigated by using miR-146b-5p inhibitor. The results demonstrated that the expression levels of miR-146b-5p were elevated in the lesions of patients with AS. In addition, the levels of miR-146b-5p in THP-1 cells stimulated with phorbol 12-myristate 13-acetate (100 nM) to induce their differentiation into macrophages were dose- and time-dependently elevated by oxidized low-density lipoprotein treatment applied for inducing foam cell formation. miR-146b-5p was also revealed to directly target tumor necrosis factor receptor-associated factor 6 (TRAF6), which functions as a signal transducer in the nuclear factor-κB (NF-κB) pathway. Furthermore, the present study reported for the first time that miR-146b-5p inhibition promotes the inflammatory response and enhances lipid uptake during foam cell formation. In conclusion, miR-146b-5p inhibition promoted chronic inflammation and had a detrimental role during AS-associated foam cell formation by targeting TRAF6.