Therapeutic effects of fibroblast growth factor‑21 against atherosclerosis via the NF‑κB pathway

Zhang,Yiming; Liu,Zhao; Zhou,Min; Liu,Changjian

doi:10.3892/mmr.2017.8100

Therapeutic effects of fibroblast growth factor‑21 against atherosclerosis via the NF‑κB pathway

Authors:
- Yiming Zhang
- Zhao Liu
- Min Zhou
- Changjian Liu
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Affiliations: Department of Vascular Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China
Published online on: November 16, 2017 https://doi.org/10.3892/mmr.2017.8100
Pages: 1453-1460
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fibroblast growth factor‑21 (FGF‑21) is a pleiotropic protein predominantly secreted in the liver, adipose tissue and pancreas. It has been reported that the metabolic hormone effects of FGF‑21 on energy metabolism are essential for human vascular endothelial cells. The aim of the present study was to investigate the therapeutic effects and the underlying primary mechanism of FGF‑21 on atherosclerosis in a rat model induced by vitamin D3 and a high fat diet. The rats with atherosclerosis were randomly divided into vehicle (PBS; negative control), FGF‑21 (6 mg/kg/d) and atorvastatin (6 mg/kg/d; positive control) groups (n=40 in each group). The rats with atherosclerosis received continuous drug or PBS administration via intravenous injection for a treatment period of 30 days, following which all animals were sacrificed. The expression levels of FGF‑21 were determined prior to and following treatment with the drug or PBS. Alterations in ultrastructure and histopathology in vascular endothelial cells were examined, and the expression of nuclear transcription factor kappa B (NF‑κB) and levels of blood lipids in the thoracic aorta tissues were also determined. The results showed that typical atheromatous plaques formed, and the mRNA and protein expression levels of FGF‑21 were lower in the vascular endothelial cells of the rats with atherosclerosis, compared with the normal rats. FGF‑21 significantly reduced blood lipids and glucose in the rats with atherosclerosis, compared with those in the PBS and atorvastatin groups (P<0.01). The expression levels of Rho kinase and NF‑κB were significantly lower in the FGF‑21 group, compared with the normal control group (P<0.01). Statistically significant differences were found in atheromatous plaques and inflammatory factors in the FGF‑21 group, compared with the PBS and atorvastatin groups (P<0.01). In conclusion, FGF‑21 significantly downregulated the levels of blood lipids, Rho kinase and NF‑κB, which contributed to atherosclerosis therapy in the model rats and indicated the potential mechanisms against atherosclerosis in the model rats.

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