Urantide improves atherosclerosis by controlling C-reactive protein, monocyte chemotactic protein-1 and transforming growth factor-β expression in rats

Zhao, Juan; Xie, Lide; Song, Chengjun; Mao, Xiaoxia; Yu, Hairong; Yu, Quan‑Xin; Ren, Liqun; Shi, Yan; Xie, Ya‐Qin; Li, Ying; Li, Shasha; Yang, Xiaohong

doi:10.3892/etm.2014.1654

Cited by 11 publications

(10 citation statements)

References 18 publications

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“…urantide (30 µg/kg; Shanghai Qiangyao Biological Technology co., ltd.) was injected into the tail veins of rats with aS in the three urantide groups daily for 3, 7 and 14 days, respectively. in the present study, the dosages of simvastatin and urantide were based on two preliminary studies by Zhao et al (10,11). The rats were given ad libitum access to food and water.…”

Section: Methodsmentioning

confidence: 99%

“…urantide, a uii receptor antagonist derived from human uii (huii), competitively antagonizes the contraction of the rat thoracic aorta and the mitogenic effect of uii on vascular smooth muscle cells (10,11). The main reason for conducting the present study was the fact that little research regarding the association between the effects of urantide on the prevention and treatment of aS and aS-related heart disease has been performed.…”

Section: Introductionmentioning

confidence: 99%

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The peptide compound urantide regulates collagen metabolism in atherosclerotic rat hearts and inhibits the JAK2/STAT3 pathway

et al. 2020

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The aim of the present study was to investigate the effect of urantide on collagen metabolism in the hearts of rats with atherosclerosis (aS) by evaluating the expression of Janus kinase 2 (JaK2)/signal transducer and activator of transcription 3 (STaT3) pathway constituents. urantide was delivered to rats with aS via tail vein injection for 3, 7 and 14 days. Serological indicators were identified by an automated biochemical analyzer. Histomorphological changes in the cardiac tissue of rats were observed by pathological staining techniques. The expression of genes and proteins was assessed using reverse transcription-quantitative Pcr and western blot analysis, respectively. localization of proteins was detected by immunofluorescence. overexpression of urotensin ii (uii) and its receptor, G protein-coupled receptor 14 (GPr14), was observed in the hearts of rats with AS and the expression of both proteins significantly declined after urantide administration. Triglyceride, total cholesterol, low-density lipoprotein, high-density lipoprotein and calcium levels were improved in rats with aS following treatment with urantide. notably, urantide was able to antagonize the uii/GPr14 system. urantide treatment resulted in markedly decreased expression levels of matrix metalloproteinase 2 (MMP-2), collagen type i/iii, and genes and proteins in the JaK2/STaT3 pathway. By contrast, TiMP metallopeptidase inhibitor 2 (TiMP-2) levels were increased. in addition, the MMP-2/TIMP-2 protein ratio was significantly decreased in rats treated with urantide compared with aS rats with no urantide treatment. constituents of the JaK2/STaT3 pathway and collagen type i/iii were found to be localized in the diseased tissue and blood vessels of the hearts of rats with aS. in conclusion, urantide was able to effectively block the uii/GPr14 system by regulating the JaK2/STaT3 pathway and collagen metabolism. inhibition of the uii/GPr14 system may prevent and potentially treat atherosclerotic myocardial fibrosis. Based on the current results, it was hypothesized that collagen metabolism may be associated with the JaK2/STaT3 pathway.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The peptide compound urantide regulates collagen metabolism in atherosclerotic rat hearts and inhibits the JAK2/STAT3 pathway

et al. 2020

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“…After 24 h of incubation, cells were washed three times with phosphate buffered solution (PBS), and 500 μL of serum-free culture medium was added to each well, followed by pretreatment using UII or urantide solution (both were prepared in PBS). The UII final concentration was 100 nM, that of urantide was 20 nM, and the dosage and usage were applied as previously described [ 24 – 26 ] with minor modifications. After half an hour, LPS solution (20 μg/mL, prepared in PBS) was used to stimulate the cells.…”

Section: Methodsmentioning

confidence: 99%

The UII/UT System Mediates Upregulation of Proinflammatory Cytokines through p38 MAPK and NF-κB Pathways in LPS-Stimulated Kupffer Cells

Liu

Liang

et al. 2015

PLoS ONE

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The urotensin II (UII)/UII receptor (UT) system is closely related to immune inflammation. In acute liver failure (ALF), the UII/UT system can promote the production and release of proinflammatory cytokines, inducing an inflammatory injury response in liver tissue. However, the mechanism by which the hepatic UII/UT system promotes proinflammatory cytokine production and release is not clear. To solve this problem, we used primary Kupffer cells (KCs) as the model system in the current study. The results showed that after lipopolysaccharide (LPS) stimulation, KCs showed significantly increased expression and release of UII/UT and proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Pretreatment with urantide, which is a UT receptor antagonist, significantly inhibited the LPS-stimulated expression and release of UII/UT, TNF-α, and IL-1β by KCs. In addition, LPS stimulation induced nuclear p38 mitogen-activated protein kinase (MAPK) protein phosphorylation and expression of the nuclear nuclear factor κB (NF-κB) p65 subunit in KCs and enhanced the binding activity of NF-κB to DNA molecules, whereas urantide pretreatment significantly inhibited the LPS-stimulated nuclear expression and activity of these molecules in KCs. Therefore, our conclusion is that the UII/UT system mediates LPS-stimulated production and release of proinflammatory cytokine by KCs, and this mediating effect at least partially relies on the inflammatory signaling pathway molecules p38 MAPK and NF-κB.

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“…A strong “UII-like” immunoreactivity was seen in coronary artery endothelial cells from patients with atherosclerosis ( 20 , 109 ), associated with a significant effect of UII on the proliferation of vascular smooth muscle cells ( 95 , 110 ) or the formation of foam cells ( 111 , 112 ). Moreover, in rat models, treatment by a UT antagonist reduces mortality and improves cardiac function after myocardial infarction ( 113 ), decreases coronary angioplasty restenosis ( 114 ), pulmonary arterial hypertension ( 115 ) and aortic inflammation, and atherosclerosis ( 116 ).…”

Section: Uii/ut System From Cardiovascular Functions To Chemokine Prmentioning

confidence: 99%

The G Protein-Coupled Receptor UT of the Neuropeptide Urotensin II Displays Structural and Functional Chemokine Features

et al. 2017

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The urotensinergic system was previously considered as being linked to numerous physiopathological states, including atherosclerosis, heart failure, hypertension, pre-eclampsia, diabetes, renal disease, as well as brain vascular lesions. Thus, it turns out that the actions of the urotensin II (UII)/G protein-coupled receptor UT system in animal models are currently not predictive enough in regard to their effects in human clinical trials and that UII analogs, established to target UT, were not as beneficial as expected in pathological situations. Thus, many questions remain regarding the overall signaling profiles of UT leading to complex involvement in cardiovascular and inflammatory responses as well as cancer. We address the potential UT chemotactic structural and functional definition under an evolutionary angle, by the existence of a common conserved structural feature among chemokine receptorsopioïdergic receptors and UT, i.e., a specific proline position in the transmembrane domain-2 TM2 (P2.58) likely responsible for a kink helical structure that would play a key role in chemokine functions. Even if the last decade was devoted to the elucidation of the cardiovascular control by the urotensinergic system, we also attempt here to discuss the role of UII on inflammation and migration, likely providing a peptide chemokine status for UII. Indeed, our recent work established that activation of UT by a gradient concentration of UII recruits Gαi/o and Gα13 couplings in a spatiotemporal way, controlling key signaling events leading to chemotaxis. We think that this new vision of the urotensinergic system should help considering UT as a chemotactic therapeutic target in pathological situations involving cell chemoattraction.

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Urantide improves atherosclerosis by controlling C-reactive protein, monocyte chemotactic protein-1 and transforming growth factor-β expression in rats

Cited by 11 publications

References 18 publications

The peptide compound urantide regulates collagen metabolism in atherosclerotic rat hearts and inhibits the JAK2/STAT3 pathway

The peptide compound urantide regulates collagen metabolism in atherosclerotic rat hearts and inhibits the JAK2/STAT3 pathway

The UII/UT System Mediates Upregulation of Proinflammatory Cytokines through p38 MAPK and NF-κB Pathways in LPS-Stimulated Kupffer Cells

The G Protein-Coupled Receptor UT of the Neuropeptide Urotensin II Displays Structural and Functional Chemokine Features

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