Fibroblast Growth Factor 21 Attenuates Vascular Calcification by Alleviating Endoplasmic Reticulum Stress Mediated Apoptosis in Rats

被引：52
作者：
Shi, Yuchen [1 ,2 ]
Wang, Shaoping [1 ,2 ]
Peng, Hongyu [1 ,2 ]
Lv, Yuan [1 ,2 ]
Li, Wenzheng [1 ,2 ]
Cheng, Shujuan [1 ,2 ]
Liu, Jinghua [1 ,2 ]
机构：
[1] Capital Med Univ, Beijing Anzhen Hosp, Dept Cardiol, 2 Anzhen Rd, Beijing 100029, Peoples R China
[2] Beijing Inst Heart Lung & Blood Vessel Dis, 2 Anzhen Rd, Beijing 100029, Peoples R China
来源：
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2019年 / 15卷 / 01期
基金：
北京市自然科学基金;
关键词：
fibroblast growth factor 21; vascular calcification; endoplasmic reticulum stress; apoptosis; SMOOTH-MUSCLE-CELLS; UNFOLDED PROTEIN RESPONSE; ER-STRESS; FGF21; ATHEROSCLEROSIS; ADIPONECTIN; SUPPRESSION; HOMEOSTASIS; EXPRESSION; INHIBITOR;
D O I：
10.7150/ijbs.28873
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Fibroblast growth factor 21 (FGF21), a hormone with multiple metabolic properties, has proven to be pleiotropic biological effects and may play pivotal role in numerous cardiovascular and metabolic diseases in the future. Vascular calcification (VC) is a concomitant pathological process of various cardiovascular and metabolic diseases. However, the effects of FGF21 on VC remain unclear. Therefore, in this research, we aimed to explore the roles and mechanisms of FGF21 in VC induced by vitamin D-3 plus nicotine (VDN) treatment rats. After 28 days VDN treatment, the calcium overload was confirmed by blood pressure, ultrasound imaging, calcium content, ALP activity and aortic pathological characteristics. In terms of FGF21, exogenous FGF21 can ameliorate the elevation of blood pressure, aortic calcification and related injury in VC rats. To investigate the mechanisms of FGF21 on VC, the endoplasmic reticulum stress (ERS) mediated apoptosis pathways were tested. As a method to detect apoptosis, the increased positive TUNEL staining cells were alleviated by FGF21 treatment. Furthermore, exogenous FGF21 can suppress the increased ERS chaperone, GRP78, in the calcified aortas. In the three pathways of ERS mediated apoptosis, we found CHOP pathway and caspase-12 pathway were involved in the treatment of FGF21, but not p-JNK/JNK pathway. Our study proved for the first time that FGF21 can inhibit the progress of VC by alleviating ERS mediated apoptosis in rats. FGF21 might be a new target for preventing and treating VC.
引用
收藏
页码：138 / 147
页数：10
相关论文
共 60 条
[41]   The role of osteoprotegerin in the crosstalk between vessels and bone: Its potential utility as a marker of cardiometabolic diseases [J].
Rochette, Luc ;
Meloux, Alexandre ;
Rigal, Eve ;
Zeller, Marianne ;
Cottin, Yves ;
Vergely, Catherine .
PHARMACOLOGY & THERAPEUTICS, 2018, 182 :115-132
[42]   FGF21 and DPP-4 inhibitor equally prevents cognitive decline in obese rats [J].
Sa-nguanmoo, Piangkwan ;
Tanajak, Pongpan ;
Kerdphoo, Sasiwan ;
Jaiwongkam, Thidarat ;
Wang, Xiaojie ;
Liang, Guang ;
Li, Xiaokun ;
Jiang, Chao ;
Pratchayasakul, Wasana ;
Chattipakorn, Nipon ;
Chattipakorn, Siriporn C. .
BIOMEDICINE & PHARMACOTHERAPY, 2018, 97 :1663-1672
[43]  
Shi Y C, 2016, Zhonghua Yi Xue Za Zhi, V96, P3741, DOI 10.3760/cma.j.issn.0376-2491.2016.46.010
[44]   Fibroblast growth factor 21 ameliorates vascular calcification by inhibiting osteogenic transition in vitamin D3 plus nicotine-treated rats [J].
Shi, Yuchen ;
Lu, Weiwei ;
Hou, Yuelong ;
Fu, Kun ;
Gan, Feng ;
Liu, Jinghua .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2018, 495 (04) :2448-2455
[45]   Fibroblast Growth Factor 21-Metabolic Role in Mice and Men [J].
Staiger, Harald ;
Keuper, Michaela ;
Berti, Lucia ;
de Angelis, Martin Hrabe ;
Haering, Hans-Ulrich .
ENDOCRINE REVIEWS, 2017, 38 (05) :468-488
[46]   The Role of Endoplasmic Reticulum Stress in the Progression of Atherosclerosis [J].
Tabas, Ira .
CIRCULATION RESEARCH, 2010, 107 (07) :839-850
[47]   Research Resource: Comprehensive Expression Atlas of the Fibroblast Growth Factor System in Adult Mouse [J].
Tacer, Klementina Fon ;
Bookout, Angie L. ;
Ding, Xunshan ;
Kurosu, Hiroshi ;
John, George B. ;
Wang, Lei ;
Goetz, Regina ;
Mohammadi, Moosa ;
Kuro-o, Makoto ;
Mangelsdorf, David J. ;
Kliewer, Steven A. .
MOLECULAR ENDOCRINOLOGY, 2010, 24 (10) :2050-2064
[48]   Magnesium Counteracts Vascular Calcification Passive Interference or Active Modulation? [J].
ter Braake, Anique D. ;
Shanahan, Catherine M. ;
de Baaij, Jeroen H. F. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2017, 37 (08) :1431-1445
[49]   Vascular smooth muscle cells and calcification in atherosclerosis [J].
Trion, A ;
van der Laarse, A .
AMERICAN HEART JOURNAL, 2004, 147 (05) :808-814
[50]   ATF4-and CHOP-Dependent Induction of FGF21 through Endoplasmic Reticulum Stress [J].
Wan, Xiao-shan ;
Lu, Xiang-hong ;
Xiao, Ye-cheng ;
Lin, Yuan ;
Zhu, Hong ;
Ding, Ting ;
Yang, Ying ;
Huang, Yan ;
Zhang, Yi ;
Liu, Yan-Long ;
Xu, Zhu-mei ;
Xiao, Jian ;
Li, Xiao-kun .
BIOMED RESEARCH INTERNATIONAL, 2014, 2014
123456