机构：[1]School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China[2]The First Affiliated Hospital of Jinan University, Guangzhou 510630, China[3]Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Anzhen Hospital of Capital Medical University, Beijing 100029, China首都医科大学附属安贞医院[4]Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, Jilin Agricultural University, Changchun 130118, China[5]State Key Laboratory of Pharmaceutical Biotechnology, the University of Hong Kong, Hong Kong, China[6]State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100730, China[7]Department of Pathophysiology, Capital Medical University, Beijing 100069, China[8]Department of Endocrinology, the 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China[9]Institute of Hypertension, Sun Yat-sen University, Guangzhou 510080, China[10]Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT 84132, USA
Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on glucose and lipid metabolism and insulin sensitivity. However, the role of FGF21 in hypertension remains elusive. Here we show that FGF21 deficiency significantly exacerbates angiotensin II-induced hypertension and vascular dysfunction, whereas such negative effects are reversed by replenishment of FGF21. Mechanistically, FGF21 acts on adipocytes and renal cells to promote induction of angiotensin-converting enzyme2 (ACE2), which in turn converts angiotensin II to angiotensin(1-7), then inhibits hypertension and reverses vascular damage. In addition, ACE2 deficiency strikingly abrogates these beneficial effects of FGF21 in mice, including alleviation of angiotensin II-associated hypertension and vascular damage. Otherwise, pharmaceutical inhibition of angiotensin-(1-7) attenuates the protective effect of FGF21 on angiotensin II-induced vascular dysfunction, but not on hypertension. Thus, FGF21 protects against angiotensin II-induced hypertension and vascular impairment by activation of the ACE2/angiotensin-(1-7) axis via fine-tuning the multi-organ crosstalk between liver, adipose tissue, kidney, and blood vessels.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81471075, 91439123]
第一作者机构：[1]School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China[2]The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
共同第一作者：
通讯作者：
通讯机构：[1]School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China[2]The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
推荐引用方式(GB/T 7714)：
Xuebo Pan,Yihui Shao,Fan Wu ,et al.FGF21 Prevents Angiotensin II-Induced Hypertension and Vascular Dysfunction by Activation of ACE2/Angiotensin-(1-7) Axis in Mice[J].CELL METABOLISM.2018,27(6):1323-+.doi:10.1016/j.cmet.2018.04.002.
APA：
Xuebo Pan,Yihui Shao,Fan Wu,,Yuan Wang,,Rongrong Xiong,...&Zhuofeng Lin.(2018).FGF21 Prevents Angiotensin II-Induced Hypertension and Vascular Dysfunction by Activation of ACE2/Angiotensin-(1-7) Axis in Mice.CELL METABOLISM,27,(6)
MLA：
Xuebo Pan,et al."FGF21 Prevents Angiotensin II-Induced Hypertension and Vascular Dysfunction by Activation of ACE2/Angiotensin-(1-7) Axis in Mice".CELL METABOLISM 27..6(2018):1323-+
生物