Proatherogenic stimuli induce HuR in atherosclerosis through MAPK/ErK pathway.

Atherosclerosis is a chronic inflammatory disease inflicting the arterial wall, and endothelial activation and dysfunction play an important role in its pathogenesis. The RNA-binding protein HuR has been associated with events of inflammation and activation in endothelial cells, however, its connection with atherosclerosis remains unclear. Here, we show that the expression and RNA-binding activity of HuR are upregulated in human and mouse atherosclerotic lesions. In addition, proatherogenic stimuli, such as inflammatory lipids (Ox-PAPC) and cytokines (TNF-α and IL-1β), induce HuR in human aortic endothelial cells (HAECs) in vitro. Moreover, HuR is also induced in mouse aorta ECs fed a high-fat diet, and the inducible degree is correlated with proatherogenic hyperlipidemia. We further show that the MAPK/ErK pathway in ECs is activated by proatherogenic stimuli in vitro and by high-fat diet in vivo. Finally, we demonstrate that the MAPK/ErK pathway is required for HuR induction by proatherogenic stimuli. Altogether, our study uncovers the inducible effect of proatherogenic stimuli on HuR in ECs, and connects this effect to the activated MAPK/ErK pathway.