Endothelial-Derived APT1-Mediated Macrophage-Endothelial Cell Interactions Participate in the Development of Atherosclerosis by Regulating the Ras/MAPK Signaling Pathway

Abstract

Acyl-protein thioesterase 1 (APT1) can affect H-Ras localization and function by promoting its depalmitoylation. However, relatively little attention has been paid to the effects of APT1 on H-Ras in the cardiovascular system. In this study, we revealed its roles in atherosclerosis development using oxidative low-density lipoprotein (ox-LDL)-induced endothelial dysfunction models and a Western diet-induced ApoE−/− mouse model. The results showed that APT1 expression was up-regulated, while that of miR-138-5p (miR-138) was down-regulated (p p < 0.05) in the ox-LDL induced endothelial dysfunction model. Meanwhile, the HUVECs-derived APT1 could further affect macrophage function through hBP transportation. Altogether, this study demonstrated that the miR-138-APT1 axis may be partially responsible for atherosclerosis development by regulating the H-Ras-MAPK signaling pathway and hBP transportation. The results also shed novel insight on the underlying mechanisms of, and identify potential diagnostic and therapeutic targets for, atherosclerotic cardiovascular diseases in the future.

Keywords

• atherosclerosis
• APT1
• miR-138-5p
• extracellular vesicles
• Ras/MAPK signaling pathway