Asprosin aggravates atherosclerosis via regulating the phenotype transformation of vascular smooth muscle cells.

Phenotype transformation of vascular smooth muscle cells (VSMCs) plays an important role in the development of atherosclerosis. Asprosin is a newly discovered adipokine, which is critical in regulating metabolism. However, the relationship between asprosin and phenotype transformation of VSMCs in atherosclerosis remains unclear. The aim of this study is to investigate whether asprosin affects the progression of atherosclerosis by inducing phenotype transformation of VSMCs. We established an atherosclerosis model in ApoE ^-/- mice and administered asprosin recombinant protein and asprosin antibody to mice. Knocking down asprosin was also as an intervention. Interestingly, we found a correlation between asprosin levels and atherosclerosis. Asprosin promoted plaque formation and phenotype transformation of VSMCs. While, Asp ^KD or asprosin antibody reduced the plaque lesion and suppressed vascular stiffness in ApoE ^-/- mice. Mechanistically, asprosin induced phenotype transformation of MOVAs by binding to GPR54, leading to Gαq/11 recruitment and activation of the PLC-PKC-ERK1/2-STAT3 signaling pathway. Si GPR54 or GPR54 antagonist partially inhibited the action of asprosin in MOVAs. Mutant GPR54-(267, 307) residue cancelled the binding of asprosin and GPR54. In summary, this study confirmed asprosin activated GPR54/Gαq/11-dependent ERK1/2-STAT3 signaling pathway, thereby promoting VSMCs phenotype transformation and aggravating atherosclerosis, thus providing a new target for the treatment of atherosclerosis.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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