title: Effects of fibroblast growth factor 21 on cell damage in vitro and atherosclerosis in vivo.
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.
authors.affiliation: a Ji Lin Medical College, Ji Lin, 132013, China.
authors.forename: Wenhe
authors.initials: W
authors.lastname: Zhu
authors.forename: Changwen
authors.initials: C
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.forename: Jianhui
authors.initials: J
authors.lastname: Cai
authors.forename: Huiyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects*; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D011994:Recombinant Proteins; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D006861:Hydrogen Peroxide
keywords: FGF-21; HUVEC; HUVECs; apoptose; apoptosis; oxidative stress; stress oxydant