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. 2020 Sep 20;19(1):207.
doi: 10.1186/s12944-020-01378-5.

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

Affiliations

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

Jue Jia et al. Lipids Health Dis. .

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.

Keywords: Adipokines; Atherosclerosis; Chemerin; Endothelial progenitor cells (EPCs); Inflammation; Lipid metabolism; MAPK pathway; Plaque.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Identification of EPCs. a Adherent cells grew in a blood island manner. Fluorescent staining of EPCs. b Adherent cells took up UEA-1-lectin. c Adherent cells took up Dil-Ac-LDL. d Adherent cells took up UEA-1-lectin and Dil-Ac-LDL. E. Surface molecular markers of EPCs. Adherent cells expressed CD34, CD133, CD14 and VEGFR-2. All experiments involving cell culture studies were repeated three times with three replicates per experiment
Fig. 2
Fig. 2
Dose-dependent effects of chemerin on the biological characteristic of EPCs. The control group was not subjected to any drug treatment; the control group received only the same volume of solvent used for the drug treatments in the treatment groups. The chemerin treatment groups included 2.5 ng/mL, 25 ng/mL, 50 ng/mL and 100 ng/mL protein-stimulated groups. EPCs were treated for 24 h. The inhibitor group was stimulated with 50 ng/mL chemerin protein plus 10 μmol/mL SB 203580. a Adherence of EPCs, a: VS. the control group, P < 0.05; b: the 50 ng/mL group VS. the inhibitor group, P < 0.05. The data are presented as the means ± SD. b Migration of EPCs, a: VS. the control group, P < 0.05; b: the 50 ng/mL group VS. the inhibitor group, P < 0.05. The data are presented as the means ± SD. c Image of EPC migration, a: the control group, b: the 2.5 ng/mL group, c: the 25 ng/mL group, d: the 50 ng/mL group, e: the 100 ng/mL group and f: the inhibitor group. d Proliferation of EPCs. The data are presented as the means ± SD. e Apoptosis ratio of EPCs. The data are presented as the median (range). All experiments involving cell culture studies were repeated three times, with three replicates per experiment
Fig. 3
Fig. 3
Time-dependent effects of chemerin on the biological characteristic of EPCs. The control group was not subjected to any drug treatment; the control group received only the same volume of solvent used for the drug treatments in the treatment groups. The chemerin treatment groups included 12 h, 24 h, 36 h and 48 h protein-stimulated groups. EPCs were treated with chemerin at a concentration of 50 ng/mL. The inhibitor group was stimulated with 50 ng/mL chemerin protein plus 10 μmol/mL SB 203580 for 24 h. a Adherence of EPCs, a: VS. the control group, P < 0.05; b: the 24 h group VS. the inhibitor group, P < 0.05. The data are presented as the means ± SD. b Migration of EPCs, a: VS. the control group, P < 0.05; b: the 24 h group VS. the inhibitor group, P < 0.05. The data are presented as the means ± SD. c Image of EPC migration, a: the control group, b: the 12 h group, c: the 24 h group, d: the 36 h group, e: the 48 h group and f: the inhibitor group. d Proliferation of EPCs. The data are presented as the means ± SD. e Apoptosis ratio of EPCs. The data are presented as the median (range). All experiments involving cell culture studies were repeated three times, with three replicates per experiment
Fig. 4
Fig. 4
Effects of chemerin on lipid parameters in ApoE−/− mice. WT mice were not treated with any drugs (n = 10). The control group (n = 6) was injected with PBS by weight, the chemerin group (n = 8) was injected with chemerin protein by weight, and the inhibitor group (n = 8) was injected with chemerin protein and the p38 MAPK-specific inhibitor SB 203580 by weight. The results are presented as the mean ± SD. a Serum T-CHO concentration. The results are expressed as the mean ± SEM. b Serum TG concentration. c Serum LDL concentration. d Serum HDL concentration. e Liver T-CHO concentration. f Liver TG concentration. g Liver LDL concentration. h Liver HDL concentration. a: VS. the WT group, P < 0.01; b: VS. the chemerin group, P < 0.01
Fig. 5
Fig. 5
Effect of chemerin on atherosclerotic plaques in ApoE−/− mice. a Oil red O staining of the aorta. b Aortic root sections in different ApoE−/− mouse groups after HE staining. c The ratio of the plaque area to the cross-section of the vessel lumen area (Control group, n = 6; Chemerin group, n = 8; Inhibitor group, n = 8). The results are presented as the mean ± SD. d The ratio of the lipid area to the plaque cross-sectional area (Control group, n = 6; Chemerin group, n = 8; Inhibitor group, n = 8). The results are presented as the mean ± SD. e Aortic root sections from different ApoE−/− mouse groups after Movat staining. f The ratio of foam cell to plaque areas (Control group, n = 6; Chemerin group, n = 8; Inhibitor group, n = 8). The results are presented as the mean ± SD. g The ratio of the proteoglycan area to the plaque area (Control group, n = 6; Chemerin group, n = 8; Inhibitor group, n = 8). a: VS. the chemerin group, P < 0.05. The results are presented as the mean ± SD. h The ratio of the collagen area to the plaque area. The results are presented as the mean ± SD
Fig. 6
Fig. 6
Effects of chemerin on the liver and kidney in ApoE−/− mice. a Oil red O staining of the liver in the four groups. b HE staining of the liver portal area. The arrows indicate inflammatory cells. c HE staining of the kidney. The arrows indicate vacuoles in the cytoplasm. d HE staining of the kidney. The arrows indicate glomeruli. e HE staining of WAT. f The sizes of adipocytes in WAT (WT group, n = 10; Control group, n = 6; Chemerin group, n = 8; Inhibitor group, n = 8). The results are presented as the mean ± SD. a: VS. the chemerin group, P < 0.05

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References

    1. Hoogeveen RM, Nahrendorf M, Riksen NP, Netea MG, de Winther M, Lutgens E, Nordestgaard BG, Neidhart M, Stroes E, Catapano AL, Bekkering S. Monocyte and haematopoietic progenitor reprogramming as common mechanism underlying chronic inflammatory and cardiovascular diseases. Eur Heart J. 2018;39:3521–3527. doi: 10.1093/eurheartj/ehx581. - DOI - PMC - PubMed
    1. Zhong S, Li L, Shen X, Li Q, Xu W, Wang X, Tao Y, Yin H. An update on lipid oxidation and inflammation in cardiovascular diseases. Free Radic Biol Med. 2019;144:266–278. doi: 10.1016/j.freeradbiomed.2019.03.036. - DOI - PubMed
    1. Siri-Tarino PW, Krauss RM. Diet, lipids, and cardiovascular disease. Curr Opin Lipidol. 2016;27:323–328. doi: 10.1097/MOL.0000000000000310. - DOI - PubMed
    1. Wong BW, Meredith A, Lin D, McManus BM. The biological role of inflammation in atherosclerosis. Can J Cardiol. 2012;28:631–641. doi: 10.1016/j.cjca.2012.06.023. - DOI - PubMed
    1. Akoumianakis I, Antoniades C. The interplay between adipose tissue and the cardiovascular system:is fat always bad? Cardiovasc Res. 2017;113(9):999–1008. doi: 10.1093/cvr/cvx111. - DOI - PubMed

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