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Effects of fibroblast growth factor 21 on cell damage in vitro and atherosclerosis in vivo
Wenhe Zhu1, Changwen Wang, Lei Liu
1a Ji Lin Medical College, Ji Lin, 132013, China.
Abstract:
Fibroblast growth factor 21 (FGF-21), which is a modulator of glucose and lipid homeostasis, acts as a novel therapeutic reagent for many metabolic perturbations. However, its potential as a treatment for cardiovascular disease, especially atherosclerosis (AS) has not been fully explored. Here, we report that recombinant FGF-21 improves resistance to cell damage from oxidative stress in vitro, and from atherosclerosis in vivo. Human umbilical vein endothelial cells (HUVECs) were induced with H2O2, followed by treatment with high purity recombinant FGF-21. The results indicated that FGF-21 significantly enhanced cell viability and decreased the degree of DNA fragmentation in HUVECs, as caused by H2O2 stress induction. Further studies revealed that FGF-21 inhibited H2O2-induced cell apoptosis by preventing the activation of mitogen-activated protein kinase (MAPK) signaling pathways. In an established rat model, FGF-21 dramatically improved the condition of atherosclerotic rats by decreasing serum levels of total triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and total cholesterol (TC), and by increasing the serum levels of high density lipoprotein cholesterol (HDL-C). FGF-21 also has antioxidant effects in the atherosclerotic rat, such that increased levels of superoxide dismutase, reduced glutathione, and reduced malondialdehyde were observed. These data provide novel insight into the potential use of FGF-21 in the prevention and treatment of human cardiovascular diseases.
Insights
Fibroblast growth factor 21 (FGF-21) protects cells from oxidative stress and improves cardiovascular health in rats. This study suggests FGF-21 as a potential therapeutic for atherosclerosis and related metabolic disorders.
Area of Science:
- Endocrinology
- Cardiovascular Research
- Molecular Biology
Background:
- Fibroblast growth factor 21 (FGF-21) regulates glucose and lipid metabolism.
- FGF-21's role in cardiovascular disease, particularly atherosclerosis (AS), is not fully understood.
Purpose of the Study:
- To investigate the therapeutic potential of recombinant FGF-21 in mitigating oxidative stress and atherosclerosis.
- To explore FGF-21's effects on endothelial cells and in an in vivo model of atherosclerosis.
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) were exposed to hydrogen peroxide (H2O2) and treated with FGF-21.
- An established rat model of atherosclerosis was used to assess FGF-21's in vivo effects.
- Biochemical assays measured cell viability, DNA fragmentation, apoptosis, lipid profiles, and antioxidant enzyme activity.
Main Results:
- FGF-21 enhanced HUVEC viability and reduced DNA fragmentation and apoptosis induced by H2O2, partly via inhibiting MAPK signaling.
- In rats, FGF-21 improved lipid profiles by decreasing triglycerides, LDL-C, and total cholesterol, while increasing HDL-C.
- FGF-21 demonstrated antioxidant effects in vivo, increasing superoxide dismutase and reduced glutathione, and decreasing malondialdehyde.
Conclusions:
- Recombinant FGF-21 confers resistance to oxidative stress in endothelial cells.
- FGF-21 exhibits significant therapeutic potential for atherosclerosis by improving lipid homeostasis and exerting antioxidant effects.
- These findings support FGF-21 as a promising candidate for preventing and treating cardiovascular diseases.
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