Chemerin enhances the adhesion and migration of human endothelial progenitor cells and increases lipid accumulation in mice with atherosclerosis

Abstract

Background The role of adipokines in the development of atherosclerosis (AS) has received increasing attention in recent years. This study aimed to explore the effects of chemerin on the functions of human endothelial progenitor cells (EPCs) and to investigate its role in lipid accumulation in ApoE-knockout (ApoE−/−) mice. Methods EPCs were cultured and treated with chemerin together with the specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB 203580 in a time- and dose-dependent manner. Changes in migration, adhesion, proliferation and the apoptosis rate of EPCs were detected. ApoE−/− mice with high-fat diet-induced AS were treated with chemerin with or without SB 203580. Weights were recorded, lipid indicators were detected, and tissues sections were stained. Results The data showed that chemerin enhanced the adhesion and migration abilities of EPCs, and reduced the apoptosis ratio and that this effect might be mediated through the p38 MAPK pathway. Additionally, chemerin increased the instability of plaques. Compared with the control group and the inhibitor group, ApoE−/− mice treated with chemerin protein had more serious arterial stenosis, higher lipid contents in plaques and decreased collagen. Lipid accumulation in the liver and kidney and inflammation in the hepatic portal area were enhanced by treatment with chemerin, and the size of adipocytes also increased after chemerin treatment. In conclusion, chemerin can enhance the adhesion and migration abilities of human EPCs and reduce the apoptosis ratio. In animals, chemerin can increase lipid accumulation in atherosclerotic plaques and exacerbate plaques instability. At the same time, chemerin can cause abnormal lipid accumulation in the livers and kidneys of model animals. After specifically blocking the p38 MAPK pathway, the effect of chemerin was reduced. Conclusions In conclusion, this study showed that chemerin enhances the adhesion and migration abilities of EPCs and increases the instability of plaques and abnormal lipid accumulation in ApoE−/− mice. Furthermore, these effects might be mediated through the p38 MAPK pathway.

AGEs/RAGE Promote Osteogenic Differentiation in Rat Bone Marrow-Derived Endothelial Progenitor Cells via MAPK Signaling

“…AGE: advanced glycation end product; CON: control; EPC: endothelial progenitor cell; OPG: osteoprotegerin; PD: PD98059; RUNX2: runt-related transcription factor 2; SB: SB203580; SP: SP600125. the P38 MAPK pathway [34]. Therefore, whether human EPCs can differentiate into osteoblasts under the stimulation of AGEs/RAGE and the signal pathway is the focus of subsequent research.…”

Circulating chemerin levels in metabolic-associated fatty liver disease: a systematic review and meta-analysis

“…Similarly, in the human hepatoma cell line HepG2, overexpression of chemerin causes lipid accumulation [ 46 ]. In addition, one study showed that the exogenous administration of chemerin increased lipid deposition not only in the liver, but also in the kidneys and arteries [ 47 ]. This potential association may be due to the relationship between chemerin and innate immunity, which in turn is inextricably linked to MAFLD [ 48 , 49 ].…”

Hepatocyte expressed chemerin-156 does not protect from experimental non-alcoholic steatohepatitis

“…Treatment of HepG2 and Huh7 cells with recombinant huChem-157 did not change cellular triglyceride and cholesterol concentrations. A further study reported that injection of recombinant chemerin in apolipoprotein E deficient mice did not alter hepatic triglyceride and cholesterol levels [ 46 ]. Altogether, the present data do not provide evidence for a role of muChem-156/huChem-157 in hepatic lipid storage.…”