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Title: Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats

Abstract

Angiotensin II (AngII) is the most important component of angiotensin, which has been regarded as a major contributor to the incidence of hypertension and vascular endothelial dysfunction. The adipocytokine C1q/TNF-related protein 6 (CTRP6) was recently reported to have multiple protective effects on cardiac and cardiovascular function. However, the exact role of CTRP6 in the progression of AngII induced hypertension and vascular endothelial function remains unclear. Here, we showed that serum CTRP6 content was significantly downregulated in SHRs, accompanied by a marked increase in arterial systolic pressure and serum AngII, CRP and ET-1 content. Then, pcDNA3.1-mediated CTRP6 delivery or CTRP6 siRNA was injected into SHRs. CTRP6 overexpression caused a significant decrease in AngII expression and AngII-mediated hypertension and vascular endothelial inflammation. In contrast, CTRP6 knockdown had the opposite effect to CTRP6 overexpression. Moreover, we found that CTRP6 positively regulated the activation of the ERK1/2 signaling pathway and the expression of peroxisome proliferator-activated receptor γ (PPARγ), a recently proven negative regulator of AngII, in the brain and vascular endothelium of SHRs. Finally, CTRP6 was overexpressed in endothelial cells, and caused a significant increase in PPARγ activation and suppression in AngII-mediated vascular endothelial dysfunction and apoptosis. The effect of that could be rescuedmore » by the ERK inhibitor PD98059. In contrast, silencing CTRP6 suppressed PPARγ activation and exacerbated AngII-mediated vascular endothelial dysfunction and apoptosis. In conclusion, CTRP6 improves PPARγ activation and alleviates AngII-induced hypertension and vascular endothelial dysfunction. - Highlights: • Serum CTRP6 was significantly decreased in spontaneously hypertensive rats (SHRs). • CTRP6 positively regulated the activation of the ERK1/2 signaling pathway. • CTRP6 negatively regulates PPARγ mediated Angiotensin II (AngII) expression. • CTRP6 alleviates AngII-induced hypertension and vascular endothelial dysfunction.« less

Authors:
 [1];  [2];  [3];  [4]; ; ;  [5];  [5];  [1]
  1. Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University (China)
  2. Department of Cardiology, The Ninth Affiliated Hospital of Medical College of Xi'an Jiaotong University (China)
  3. Affiliated Xi'an Honghui Hospital of Medical College of Xi'an Jiaotong University (China)
  4. Department of Gereology, The Ninth Affiliated Hospital of Medical College of Xi'an Jiaotong University (China)
  5. Departments of Cardiology, The 451st Hospital of People's Liberation Army (China)
Publication Date:
OSTI Identifier:
22696774
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 482; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANGIOTENSIN; HYPERTENSION; INHIBITION; RATS

Citation Formats

Chi, Liyi, Departments of Cardiology, The 451st Hospital of People's Liberation Army, Hu, Xiaojing, Zhang, Wentao, Bai, Tiao, Zhang, Linjing, Zeng, Hua, Guo, Ruirui, Zhang, Yanhai, and Tian, Hongyan. Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2016.11.102.
Chi, Liyi, Departments of Cardiology, The 451st Hospital of People's Liberation Army, Hu, Xiaojing, Zhang, Wentao, Bai, Tiao, Zhang, Linjing, Zeng, Hua, Guo, Ruirui, Zhang, Yanhai, & Tian, Hongyan. Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats. United States. doi:10.1016/J.BBRC.2016.11.102.
Chi, Liyi, Departments of Cardiology, The 451st Hospital of People's Liberation Army, Hu, Xiaojing, Zhang, Wentao, Bai, Tiao, Zhang, Linjing, Zeng, Hua, Guo, Ruirui, Zhang, Yanhai, and Tian, Hongyan. Sun . "Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats". United States. doi:10.1016/J.BBRC.2016.11.102.
@article{osti_22696774,
title = {Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats},
author = {Chi, Liyi and Departments of Cardiology, The 451st Hospital of People's Liberation Army and Hu, Xiaojing and Zhang, Wentao and Bai, Tiao and Zhang, Linjing and Zeng, Hua and Guo, Ruirui and Zhang, Yanhai and Tian, Hongyan},
abstractNote = {Angiotensin II (AngII) is the most important component of angiotensin, which has been regarded as a major contributor to the incidence of hypertension and vascular endothelial dysfunction. The adipocytokine C1q/TNF-related protein 6 (CTRP6) was recently reported to have multiple protective effects on cardiac and cardiovascular function. However, the exact role of CTRP6 in the progression of AngII induced hypertension and vascular endothelial function remains unclear. Here, we showed that serum CTRP6 content was significantly downregulated in SHRs, accompanied by a marked increase in arterial systolic pressure and serum AngII, CRP and ET-1 content. Then, pcDNA3.1-mediated CTRP6 delivery or CTRP6 siRNA was injected into SHRs. CTRP6 overexpression caused a significant decrease in AngII expression and AngII-mediated hypertension and vascular endothelial inflammation. In contrast, CTRP6 knockdown had the opposite effect to CTRP6 overexpression. Moreover, we found that CTRP6 positively regulated the activation of the ERK1/2 signaling pathway and the expression of peroxisome proliferator-activated receptor γ (PPARγ), a recently proven negative regulator of AngII, in the brain and vascular endothelium of SHRs. Finally, CTRP6 was overexpressed in endothelial cells, and caused a significant increase in PPARγ activation and suppression in AngII-mediated vascular endothelial dysfunction and apoptosis. The effect of that could be rescued by the ERK inhibitor PD98059. In contrast, silencing CTRP6 suppressed PPARγ activation and exacerbated AngII-mediated vascular endothelial dysfunction and apoptosis. In conclusion, CTRP6 improves PPARγ activation and alleviates AngII-induced hypertension and vascular endothelial dysfunction. - Highlights: • Serum CTRP6 was significantly decreased in spontaneously hypertensive rats (SHRs). • CTRP6 positively regulated the activation of the ERK1/2 signaling pathway. • CTRP6 negatively regulates PPARγ mediated Angiotensin II (AngII) expression. • CTRP6 alleviates AngII-induced hypertension and vascular endothelial dysfunction.},
doi = {10.1016/J.BBRC.2016.11.102},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 482,
place = {United States},
year = {2017},
month = {1}
}