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C1q/TNF-α--Related Protein 1 (CTRP1) Maintains Blood Pressure Under Dehydration Conditions

Authors
 Sora Han  ;  Ae Lee Jeong  ;  Sunyi Lee  ;  Jeong Su Park  ;  Sumiyasuren Buyanravjikh  ;  Wonku Kang  ;  Seungmok Choi  ;  Changmin Park  ;  Jin Han  ;  Woo-Chan Son  ;  Kyung Hyun Yoo  ;  Jae Hoon Cheong  ;  Goo Taeg Oh  ;  Won-Young Lee  ;  Jongwan Kim  ;  Suk Hyo Suh  ;  Sang-Hak Lee  ;  Jong-Seok Lim  ;  Myeong-Sok Lee  ;  Young Yang 
Citation
 Circulation Research, Vol.123(5) : e5-e19, 2018 
Journal Title
 Circulation Research 
ISSN
 0009-7330 
Issue Date
2018
Keywords
CTRP1 ; dehydration ; glucocorticoid ; hypertension, high blood pressure ; vasoconstriction
Abstract
Rationale: Circulating C1q/TNF-α-related protein 1 (CTRP1) levels are increased in hypertensive patients compared to in healthy subjects. Nonetheless, little is known about the molecular and physiological function of CTRP1 in blood pressure (BP) regulation. Objective: To investigate the physiological/pathophysiological role of CTRP1 in BP regulation. Methods and Results: CTRP1 production was increased to maintain normotension under dehydration conditions, and this function was impaired in inducible CTRP1 knockout mice (CTRP1ΔCAG). The increase in CTRP1 under dehydration conditions was mediated by glucocorticoids, and the antagonist mifepristone prevented the increase in CTRP1 and attenuated BP recovery. Treatment with a synthetic glucocorticoid increased the transcription, translation, and secretion of CTRP1 from skeletal muscle cells. Functionally, CTRP1 increases BP through the stimulation of the angiotensin II receptor 1 (AT1R)-Ras homolog gene family (Rho)/Rho kinase (ROCK) signaling pathway to induce vasoconstriction. CTRP1 promoted AT1R plasma membrane trafficking through phosphorylation of AKT and AKT substrate of 160 kDa (AS160). In addition, the administration of an AT1R blocker, losartan, recovered the hypertensive phenotype of CTRP1 transgenic (TG) mice. Conclusions: For the first time, we provide evidence that CTRP1 contributes to the regulation of BP homeostasis by preventing dehydration-induced hypotension.
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DOI
10.1161/CIRCRESAHA.118.312871
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
박정수(Park, Jeong Su) ORCID logo https://orcid.org/0000-0003-4551-4294
이상학(Lee, Sang Hak) ORCID logo https://orcid.org/0000-0002-4535-3745
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/163519
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