Nesfatin‐1 inhibits cerebral aneurysms by activating Nrf2 and inhibiting NF‐κB signaling

Abstract

AbstractAimsCerebral aneurysm (CA) has been considered one of the most common cerebrovascular diseases, affecting millions of people worldwide. A therapeutic agent is currently missing for the treatment of CA. Nesfatin‐1 (Nes‐1) is an 82‐amino acid adipokine which possesses a wide range of biological functions. However, the physiological function of Nes‐1 in CA is still unknown. Here, we aimed to assess the preventive effects of Nes‐1 in the pathological development of CA and elucidate the mechanisms behind this.MethodsWe used an elastase‐induced CA model, accompanied by a high‐salt diet to induce hypertension. Additionally, diverse experimental techniques, including Verhoeff‐Van Gieson staining, real time PCR, enzyme‐linked immuno sorbent assay (ELISA), and immunofluorescence staining, were employed to assess CA formation, gene and protein expression, as well as the macrophage infiltration.ResultsOur results indicate that administration of Nes‐1 significantly decreased the aneurysm size. Additionally, Nes‐1 prevented inflammatory response by inhibiting the expression of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and monocyte chemoattractant protein 1 (MCP‐1) at both the mRNA and protein levels in the Circle of Willis (COW) region. Also, the increased levels of matrix metalloproteinase‐2 (MMP‐2) and matrix metalloproteinase‐9 (MMP‐9) in the COW region were reduced by Nes‐1. We found that Nes‐1 administration suppressed the invasion of macrophages. Mechanistically, Nes‐1 activated Nrf‐2 by promoting its nuclear translocation but prevented the activation of the IκBα/NF‐κB signaling pathway.ConclusionThese findings suggest that Nes‐1 might be used as a promising agent for the prevention of CA.