caa a22 4500 606221352 CHVBK 20210128101128.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00380-014-0557-9 doi (NATIONALLICENCE)springer-10.1007/s00380-014-0557-9 Possible role of fibroblast growth factor 21 on atherosclerosis via amelioration of endoplasmic reticulum stress-mediated apoptosis in apoE−/− mice [Elektronische Daten] [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] 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 4weeks 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. Springer Japan, 2014 Fibroblast growth factor 21 nationallicence Atherosclerosis nationallicence Apoptosis nationallicence Endoplasmic reticulum stress nationallicence Wu Xi Department of Cardiology, Fuwai Hospital and National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, 100037, Beijing, China aut Qi Yong-Fen Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, 100191, Beijing, China aut Chang Jin-Rui Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, 100191, Beijing, China aut Lu Wei-Wei Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, 100191, Beijing, China aut Zhang Jin-Sheng Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, 100191, Beijing, China aut Wang Shao-Ping Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut Cheng Shu-Juan Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut Zhang Ming Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut Fan Qian Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut Lv Yuan Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut Zhu Hui Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut Xin Man-Kun Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut Lv Yun Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut Liu Jing-Hua Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut Heart and Vessels Springer Japan 30/5(2015-09-01), 657-668 0910-8327 30:5<657 2015 30 380 https://doi.org/10.1007/s00380-014-0557-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00380-014-0557-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wu Xi Department of Cardiology, Fuwai Hospital and National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, 100037, Beijing, China aut NATIONALLICENCE 700 1- Qi Yong-Fen Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, 100191, Beijing, China aut NATIONALLICENCE 700 1- Chang Jin-Rui Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, 100191, Beijing, China aut NATIONALLICENCE 700 1- Lu Wei-Wei Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, 100191, Beijing, China aut NATIONALLICENCE 700 1- Zhang Jin-Sheng Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, 100191, Beijing, China aut NATIONALLICENCE 700 1- Wang Shao-Ping Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut NATIONALLICENCE 700 1- Cheng Shu-Juan Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut NATIONALLICENCE 700 1- Zhang Ming Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut NATIONALLICENCE 700 1- Fan Qian Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut NATIONALLICENCE 700 1- Lv Yuan Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut NATIONALLICENCE 700 1- Zhu Hui Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut NATIONALLICENCE 700 1- Xin Man-Kun Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut NATIONALLICENCE 700 1- Lv Yun Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut NATIONALLICENCE 700 1- Liu Jing-Hua Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, 2 Anzhen Road, Chaoyang District, 100029, Beijing, China aut NATIONALLICENCE 773 0- Heart and Vessels Springer Japan 30/5(2015-09-01), 657-668 0910-8327 30:5<657 2015 30 380