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.

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