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, AspKD 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. [Display omitted] •Plasma asprosin level increased in atherosclerotic patients and mice.•Asprosin induces phenotype transformation of VSMCs from contractile phenotype to synthetic phenotype.•Asprosin binds to GPR54 and then couples Gαq/11, thereby initiating intracellular ERK1/2-STAT3 signaling cascade in VSMCs.•Asprosin deficiency in adipose tissue or asprosin antibody reduces plaque, inhibits phenotype transformation of VSMCs.•Asprosin is expected to be a marker for early clinical diagnosis of atherosclerosis.