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 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.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, China; Departments of Cardiology, The 451st Hospital of People's Liberation Army, China.
authors.forename: Liyi
authors.initials: L
authors.lastname: Chi
authors.affiliation: Department of Cardiology, The Ninth Affiliated Hospital of Medical College of Xi'an Jiaotong University, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Hu
authors.affiliation: Affiliated Xi'an Honghui Hospital of Medical College of Xi'an Jiaotong University, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Gereology, The Ninth Affiliated Hospital of Medical College of Xi'an Jiaotong University, China.
authors.forename: Tiao
authors.initials: T
authors.lastname: Bai
authors.affiliation: Departments of Cardiology, The 451st Hospital of People's Liberation Army, China.
authors.forename: Linjing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Departments of Cardiology, The 451st Hospital of People's Liberation Army, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Departments of Cardiology, The 451st Hospital of People's Liberation Army, China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Guo
authors.affiliation: Departments of Cardiology, The 451st Hospital of People's Liberation Army, China. Electronic address: yanhaizhangxian@163.com.
authors.forename: Yanhai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, China. Electronic address: hytgxy@163.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Tian
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism; D002469:Cell Separation; D003331:Coronary Vessels / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005419:Flavonoids / Q000737:chemistry; D005434:Flow Cytometry; D020868:Gene Silencing; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D054392:Adipokines; C000619951:C1qtnf6 protein, rat; D005419:Flavonoids; D047495:PPAR gamma; D034741:RNA, Small Interfering; D000804:Angiotensin II; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Adipocytokine; Angiotensin II; C1q/TNF-related protein 6; Hypertension; PPARγ activation; Vascular endothelial dysfunction