Erschienen in:
01.09.2015 | Original Article
Possible role of fibroblast growth factor 21 on atherosclerosis via amelioration of endoplasmic reticulum stress-mediated apoptosis in apoE−/− mice
verfasst von:
Xi Wu, Yong-Fen Qi, Jin-Rui Chang, Wei-Wei Lu, Jin-Sheng Zhang, Shao-Ping Wang, Shu-Juan Cheng, Ming Zhang, Qian Fan, Yuan Lv, Hui Zhu, Man-Kun Xin, Yun Lv, Jing-Hua Liu
Erschienen in:
Heart and Vessels
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Ausgabe 5/2015
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Abstract
Fibroblast growth factor 21 (FGF-21) is an endocrine factor that can be secreted into circulation by the liver. FGF-21 takes part in metabolic actions and is thought to be a promising candidate for the treatment of diabetes. However, the role of FGF-21 in atherosclerosis is unknown. In this study, apoE−/− mice were fed an atherogenic diet for 4 weeks with and without subcutaneous injections of FGF-21. ApoE−/− mice fed an atherogenic diet showed hyperlipidemia, a large plaque area in aortas and increased vessel wall thickness. Plasma FGF-21 content and protein level of FGF receptor 1 (FGFR1) in aortas was greater in apoE−/− than C57BL/6J mice. Exogenous FGF-21 treatment significantly ameliorated dyslipidemia in apoE−/− mice. FGF-21–treated apoE−/− mice showed reduced number of aortic plaques and plaque area as well as reduced number of TUNEL-positive cells. Protein levels of the endoplasmic reticulum stress markers glucose-regulated protein 94, caspase-12 and C/EBP homologous protein were reduced by 34.5, 31.4 and 26.5 %, respectively, in apoE−/− mice. Endogenous expression of FGF-21 and its receptor FGFR1 were upregulated in apoE−/− mice, and exogenous administration of FGF-21 ameliorated the atherogenic-induced dyslipidemia and vascular atherosclerotic lesions. FGF-21 protecting against atherosclerosis might be in part by its inhibitory effects on endoplasmic reticulum stress-mediated apoptosis.