ZIP8 induces monocyte adhesion to the aortas ex-vivo by regulating zinc influx.

Abstract

Monocytes recruited and adhering to the inflamed arteries are crucial for atherosclerosis development. Here, we report the role of zinc (Zn) homeostasis in monocyte adhesion and recruitment. By comparing the expression levels of Zntransporters between non-adhering and adhering monocytes, we found that the Znimporter ZIP8 was specifically upregulated in monocytes adhering to the aortas ex-vivo. Although the overexpression of ZIP8 increased the absorption of Zn, Feand Cdin monocytes, only Znsupplementation was demonstrated capable of promoting the adhesion of monocytes to endothelial monolayers in vitro. In addition, we confirmed the role of ZIP8-dependent Zninflux in promoting monocyte adhesion to the aortas ex-vivo. More importantly, the enforced expression of ZIP8 increased monocyte adhesion and recruitment to the nascent atherosclerotic lesions in ApoEmice. Overall, our results suggest that the Zninflux in monocytes regulated by ZIP8 is a novel factor determining their adhesion and recruitment to atherosclerotic lesions, and that targeting ZIP8 or Znhomeostasis may represent a novel strategy to interfere these activities.