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

Chi, Liyi; Hu, Xiaojing; Zhang, Wentao; Bai, Tiao; Zhang, Linjing; Zeng, Hongyu; Guo, Ruirui; Zhang, Yanhai; Tian, Hui

doi:10.1016/j.bbrc.2016.11.102

Cited by 31 publications

(21 citation statements)

References 28 publications

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“…This effect was mediated through the upregulation of eNOS, elevation of NO, and regulation of PKC signaling pathways [ 38 ]. PPARγ, on the other hand, holds antioxidant and anti-inflammatory effects in endothelium [ 37 ] and has been shown to counteract Ang II-induced endothelial dysfunction [ 39 ]. For instance, overexpression of an adipokine, CTRP6 in spontaneously hypertensive rats (SHRs) decreased Ang II expression, alleviated Ang II-induced hypertension and endothelial dysfunction, and increased p-PPARγ and p-ERK1/2 protein levels in the brain, suggesting that the protective effects of CTRP6 are mediated through ERK signaling and PPARγ activation [ 39 ].…”

Section: Endotheliummentioning

confidence: 99%

Impact of the Renin–Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives

Noureddine

Altara

Fan

et al. 2020

IJMS

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The effects of the renin–angiotensin system (RAS) surpass the renal and cardiovascular systems to encompass other body tissues and organs, including the brain. Angiotensin II (Ang II), the most potent mediator of RAS in the brain, contributes to vascular dementia via different mechanisms, including neuronal homeostasis disruption, vascular remodeling, and endothelial dysfunction caused by increased inflammation and oxidative stress. Other RAS components of emerging significance at the level of the blood–brain barrier include angiotensin-converting enzyme 2 (ACE2), Ang(1–7), and the AT2, Mas, and AT4 receptors. The various angiotensin hormones perform complex actions on brain endothelial cells and pericytes through specific receptors that have either detrimental or beneficial actions. Increasing evidence indicates that the ACE2/Ang(1–7)/Mas axis constitutes a protective arm of RAS on the blood–brain barrier. This review provides an update of studies assessing the different effects of angiotensins on cerebral endothelial cells. The involved signaling pathways are presented and help highlight the potential pharmacological targets for the management of cognitive and behavioral dysfunctions associated with vascular dementia.

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Section: Endotheliummentioning

confidence: 99%

Impact of the Renin–Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives

Noureddine

Altara

Fan

et al. 2020

IJMS

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“…Data derived from studies on KO models and overexpression showed contradictory role of CTRP6 in regard to inflammatory process. On one hand, it induces the expression of interleukin‐10 in macrophages, inhibits tumor growth factor‐β‐induced fibrogenesis, alleviates inflammatory pathology in rheumatoid arthritis mouse model, decreases hs‐CRP levels, and ameliorates angiotensin‐II‐induced hypertension and vascular dysfunction in endothelial cells . On the other hand, CTRP6 exhibits pro‐inflammatory functions, unlike its close homolog—adiponectin.…”

Section: Discussionmentioning

confidence: 99%

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

et al. 2020

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Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting females of reproductive age. It has been associated with cardiometabolic disorders including diabetes mellitus and cardiovascular disorders, and increases the risk of developing fecundity pathologies including recurrent pregnancy loss (RPL) and infertility. C1q/tumor necrosis factor‐α‐related protein‐6 (CTRP6) is a novel adipokine involved in glucose and lipid metabolism, host inflammation, and organogenesis. In the present study, we aimed to determine the association of serum CTRP6 levels with some components of metabolic syndrome in PCOS patients (infertile PCOS [inf‐PCOS] and PCOS‐RPL). This case–control study included 120 PCOS patients (60 inf‐PCOS and 60 PCOS‐RPL) and 60 healthy controls. Serum high‐sensitivity C‐reactive protein (hs‐CRP) and homocysteine were measured using commercial kits, while adiponectin and CTRP6 levels were assessed using ELISA technique. Inf‐PCOS and PCOS‐RPL individuals had higher levels of serum CTRP6 than controls (546.15 ± 125.02 ng/ml and 534.04 ± 144.19 ng/ml vs. 440.16 ± 159.24 ng/ml; both p < .001). Moreover, serum adiponectin levels were significantly reduced, while fasting insulin, homeostasis model assessment of insulin resistance, free testosterone, and hs‐CRP levels were significantly elevated in PCOS group, when compared with controls. Furthermore, serum CTRP6 positively associated with body mass index in all subjects. It showed an inverse correlation with adiponectin in PCOS group and subgroups. However, it had a direct association with hs‐CRP in PCOS group and inf‐PCOS subgroup, but not PCOS‐RPL subgroup. These findings unravel a probable role of CTRP6 in PCOS pathogenesis, which poses a possibility to be a good diagnostic target. However, further investigation is needed.

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“…It is expressed mainly in adipose tissue, the heart, the brain, and so on, and is secreted into the blood as a multimeric complex [7]. Previous studies have shown that CTRP6 regulates endothelial cell function and angiotensin II induced hypertension, myofibroblast, myocardial fibrosis, fat differentiation and fibrogenesis [9][10][11][12][13][14][15]. Wong et al reported that CTRP6 expression was elevated in the fat tissues of ob/ ob and adiponectin KO mice fed an high fat diet (HFD).…”

Section: Introductionmentioning

confidence: 99%

Circulating CTRP6 Levels are Increased in Overweight or Obese Chinese Individuals and Associated with Insulin Resistance Parameters: A Pilot Study

Liao

Tang

et al. 2019

Exp Clin Endocrinol Diabetes

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Aims CTRP6, a newly discovered adipokine, has been found to be a regulator for energy homeostasis. However, the association between circulating CTRP6 and obesity in humans is still unclear. Methods 256 individuals, including 185 overweight/obese (OW/OB) and 71 normal weight adults, were recruited for this study. Circulating concentrations of CTRP6 and adiponectin (Adipoq) were examined by ELISA. Results Serum CTRP6 levels in obese individuals were significantly increased compared with those in healthy individuals (506.1±134.9 vs.363.3±80.5 ng/mL, P<0.01). Conversely, serum Adipoq concentrations in OW/OB individuals were markedly decreased compared with healthy controls [20.8 (12.1–29.3) vs. 14.1 ( 8.61–17.7) ; P<0.01]. Correlation analysis revealed that there was a positive relationship between circulating CTRP6 and age, BMI, Fat%, LDL-C, TG, WHR, TC, FBG, FIns, HOMA-IR and HbA1c, but there was an inverse correlation with Adipoq and HDL-C. Logistic regression analysis revealed that high serum CTRP6 levels are markedly associated with OW/OB. Finally, ROC curve analysis showed that the cut-off value for serum CTRP6 for prediction of IR is 518 ng/mL. Conclusions CTRP6 may be a marker related to OW/OB.

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

Cited by 31 publications

References 28 publications

Impact of the Renin–Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives

Impact of the Renin–Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

Circulating CTRP6 Levels are Increased in Overweight or Obese Chinese Individuals and Associated with Insulin Resistance Parameters: A Pilot Study

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