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

Monocytes recruited and adhering to the inflamed arteries are crucial for atherosclerosis development. Here, we report the role of zinc (Zn2+) homeostasis in monocyte adhesion and recruitment. By comparing the expression levels of Zn2+ transporters between non-adhering and adhering monocytes, we found that the Zn2+ importer ZIP8 was specifically upregulated in monocytes adhering to the aortas ex-vivo. Although the overexpression of ZIP8 increased the absorption of Zn2+, Fe2+ and Cd2+ in monocytes, only Zn2+ supplementation was demonstrated capable of promoting the adhesion of monocytes to endothelial monolayers in vitro. In addition, we confirmed the role of ZIP8-dependent Zn2+ influx 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 ApoE−/− mice. Overall, our results suggest that the Zn2+ influx in monocytes regulated by ZIP8 is a novel factor determining their adhesion and recruitment to atherosclerotic lesions, and that targeting ZIP8 or Zn2+ homeostasis may represent a novel strategy to interfere these activities.