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

Title
C1q/TNF-alpha-Related Protein 1 (CTRP1) Maintains Blood Pressure Under Dehydration Conditions
Authors
Han, SoraJeong, Ae LeeLee, SunyiPark, Jeong SuBuyanravjikh, SumiyasurenKang, WonkuChoi, SeungmokPark, ChangminHan, JinSon, Woo-ChanYoo, Kyung HyunCheong, Jae HoonOh, Goo TaegLee, Won-YoungKim, JongwanSuh, Suk HyoLee, Sang-HakLim, Jong-SeokLee, Myeong-SokYang, Young
Ewha Authors
서석효오구택
SCOPUS Author ID
서석효scopus; 오구택scopus
Issue Date
2018
Journal Title
CIRCULATION RESEARCH
ISSN
0009-7330JCR Link1524-4571JCR Link
Citation
vol. 123, no. 5, pp. E5 - E19
Keywords
dehydrationglucocorticoidshypertensionmicevasoconstriction
Publisher
LIPPINCOTT WILLIAMS & WILKINS
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
Rationale: Circulating CTRP1 (C1q/TNF-alpha [tumor necrosis factor-alpha]-related protein 1) levels are increased in hypertensive patients compared with those 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 KO (knockout) mice (CTRP1(Delta CAG)). 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 AT1R (Ang II [angiotensin II] receptor 1)-Rho (Ras homolog gene family)/ROCK (Rho kinase)-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 TG (transgenic) mice. Conclusions: For the first time, we provide evidence that CTRP1 contributes to the regulation of BP homeostasis by preventing dehydration-induced hypotension.
DOI
10.1161/CIRCRESAHA.118.312871
Appears in Collections:
의과대학 > 의학과 > Journal papers
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