Unveiling the therapeutic potential of miR-146a: Targeting innate inflammation in atherosclerosis

Abstract

Atherosclerosis is the foremost vascular disease, precipitating debilitating complications. Although therapeutic strategies have historically focused on reducing cholesterol deposition, recent insights emphasize the pivotal role of inflammation. Innate inflammation significantly contributes to plaque instability and rupture, underscoring the need for intervention across all disease stages. Numerous studies have highlighted the therapeutic potential of targeting innate immune pathways in atherosclerosis, revealing significant advancements in understanding the molecular mechanisms underlying inflammatory processes within arterial lesions. Notably, research has demonstrated that the modulation of microRNA-146a (miR-146a) expression impacts innate inflammation, effectively halts atherosclerosis progression, and enhances plaque stability by targeting interleukin-1 receptor-associated kinase (IRAK) and activating TNF receptor-associated factor 6 (TRAF6), a signalling pathway involving toll-like receptors (TLRs). Understanding the intricate mechanisms involved is crucial. This study provides a comprehensive analysis of the evidence and underlying mechanisms through which miR-146a exerts its effects. Integrating these findings into clinical practice may herald a transformative era in managing atherosclerotic cardiovascular disease.

Keywords: atherosclerosis; cardiovascular; inflammation; miR‐146a; plaque.

FIGURE 1

The role of miR‐146a as a molecular brake of inflammation in atherosclerosis. miR‐146a exerts an inhibitory role in the TLR signalling pathway by suppressing the activation of IRAK and TRAF6. Additionally, it negatively regulates proinflammatory cytokine production, monocyte recruitment, and the progression of atherosclerosis. IRAK, interleukin‐1 receptor‐associated kinase; MyD88, myeloid differentiation primary‐response protein 88; NF‐KB, nuclear factor kappa B; TLR, toll‐like receptors; TRAF6, tumour necrosis factor receptor‐associated factor 6.