C1q/TNF-alpha-Related Protein 1 (CTRP1) Maintains Blood Pressure Under Dehydration Conditions
- 주제(키워드) dehydration , glucocorticoids , hypertension , mice , vasoconstriction
- 주제(기타) Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease
- 설명문(일반) [Han, Sora] Sookmyung Womens Univ, Res Inst Womens Hlth, Seoul, South Korea; [Buyanravjikh, Sumiyasuren; Yoo, Kyung Hyun; Lim, Jong-Seok; Lee, Myeong-Sok; Yang, Young] Sookmyung Womens Univ, Dept Biol Sci, Seoul, South Korea; [Jeong, Ae Lee] Osong Med Innovat Fdn, New Drug Dev Ctr, Osan, South Korea; [Lee, Sunyi] CJ HealthCare, Res & Dev Ctr, Icheon, South Korea; [Park, Jeong Su] Yonsei Univ, Coll Med, Yonsei Biomed Res Inst, Severance Biomed Sci Inst, Seoul, South Korea; [Lee, Sang-Hak] Yonsei Univ, Coll Med, Severance Hosp, Dept Internal Med,Div Cardiol, Seoul, South Korea; [Kang, Wonku; Choi, Seungmok; Park, Changmin] Chung Ang Univ, Coll Pharm, Seoul, South Korea; [Han, Jin] Inje Univ, Cardiovasc & Metab Dis Ctr, Coll Med, Natl Res Lab Mitochondrial Signaling,Dept Physiol, Busan, South Korea; [Son, Woo-Chan] Univ Ulsan, Coll Med, Asan Med Ctr, Pathol Dept, Seoul, South Korea; [Cheong, Jae Hoon] Sahmyook Univ, Dept Pharm, Seoul, South Korea; [Oh, Goo Taeg] Ewha Womans Univ, Dept Life Sci, Seoul, South Korea; [Suh, Suk Hyo] Ewha Womans Univ, Med Sch, Dept Physiol, Seoul, South Korea; [Lee, Won-Young] Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Dept Endocrinol, Seoul, South Korea; [Lee, Won-Young] Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Dept Metab, Seoul, South Korea; [Kim, Jongwan] Dankook Univ, Sch Med, Dept Lab Med, Cheonan, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 LIPPINCOTT WILLIAMS & WILKINS
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000156109
- 본문언어 영어
- Published As http://dx.doi.org/10.1161/CIRCRESAHA.118.312871
초록/요약
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.
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