Publication date: Available online 26 April 2018
Source:Cell Metabolism
Author(s): Xuebo Pan, Yihui Shao, Fan Wu, Yuan Wang, Rongrong Xiong, Jujia Zheng, Haishan Tian, Baile Wang, Yanfang Wang, Yi Zhang, Zongsheng Han, Aijuan Qu, Haixia Xu, Aihua Lu, Tianxin Yang, Xiaokun Li, Aimin Xu, Jie Du, Zhuofeng Lin
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 enzyme 2 (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.
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Teaser
Pan et al. show that the metabolic hormone fibroblast growth factor 21 (FGF21) plays an important role in blood pressure regulation by counteracting angiotensin II-induced hypertension and vessel injury. Mechanistically, FGF21 acts on adipocytes and renal cells to promote induction of ACE2, a carboxypeptidase that metabolizes angiotensin II to angiotensin-(1–7).https://ift.tt/2KhZHNu
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