Fibroblast growth factor 21 attenuates inflammation and oxidative stress in atherosclerotic rat via enhancing the Nrf1-ARE signaling pathway.

ABSTRACT

Inflammation and oxidative stress are associated with atherosclerotic progression. Fibroblast growth factor 21 (FGF21), a regulator of energy metabolism, has been reported to suppress the pathogenesis of atherosclerosis. However, the mechanism of anti-atherosclerotic effects of FGF21 remains unclear and needs to be further investigated. Transcription factor NF-E2-related 2 (Nrf2), a sensitive regulator of oxidative stress, is also associated with atherosclerotic progression. In this study, we investigated whether up-regulation of FGF21 affected inflammation and oxidative stress in atherosclerotic rats and whether the Nrf2-signaling pathway was involved in FGF21-mediated effects. Pathological changes were detected in arterial tissues of rats, and the expression of inflammatory and oxidative stress indicators, vascular endothelial markers, and Nrf2-signaling related protein were measured in the serum or/and arterial tissues of rats. As a result, expression of FGF21 and Nrf2-ARE signaling related proteins were markedly suppressed in arterial tissues of model rats. Thickness of endarteria and infiltrating cells obviously increased in atherosclerotic rats, whereas the increase of FGF21 expression could decrease thickness of endarteria. Moreover, the levels of ET-1, MDA, MCP-1, ICAM-1 and VCAM-1 were significantly higher in model rats than that in normal rats, whereas the levels of NO, GSH and T-AOC were significantly lower. Compared with model rats, up-regulation of FGF21 could increase the expression of Nrf2-ARE signaling related proteins and the level of anti-oxidative indicators, decrease the levels of endothelial dysfunction, and reduce inflammatory indicators. Down-regulation of FGF21 could reverse these actions. Therefore FGF21 reduces inflammation and oxidative stress in atherosclerotic rats via Nrf2-ARE signaling pathway.