Urotensin II receptor antagonist reduces hepatic resistance and portal pressure through enhanced eNOS-dependent HSC vasodilatation in CCl4-induced cirrhotic rats

Zhang, Ruoxi; Chen, Jing; Liu, Diangang; Wang, Yu

doi:10.1007/s11684-019-0689-5

Cited by 11 publications

(4 citation statements)

References 38 publications

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“…Among the selected proteins within the panel, UTS2R, a ligand‐binding receptor, has been reported to correlate with liver cirrhosis and portal hypertension. Notably, a report showed the antagonist of UTS2R could reduce hepatic resistance and portal hypertension 41 . Consistent with 82 proteins identified by SomaScan, the major representation of the proteins (PYGL, HMGCS1, MPST and GPD1) were involved with lipid metabolism or glycerophospholipid metabolism.…”

Section: Discussionsupporting

confidence: 68%

“…Notably, a report showed the antagonist of UTS2R could reduce hepatic resistance and portal hypertension. 41 Consistent with 82 proteins identified by SomaScan, the major representation of the proteins (PYGL, HMGCS1, MPST and GPD1) were involved with lipid metabolism or glycerophospholipid metabolism. The second group of proteins (GZMA, CFHR5 and RPS6KA1) were related to immune response.…”

Section: Discussionsupporting

confidence: 67%

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Non‐invasive candidate protein signature predicts hepatic venous pressure gradient reduction in cirrhotic patients after sustained virologic response

Richards

Guo²,

Zou³

et al. 2023

Liver International

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Background and AimsA reduction in hepatic venous pressure gradient (HVPG) is the most accurate marker for assessing the severity of portal hypertension and the effectiveness of intervention treatments. This study aimed to evaluate the prognostic potential of blood‐based proteomic biomarkers in predicting HVPG response amongst cirrhotic patients with portal hypertension due to Hepatitis C virus (HCV) and had achieved sustained virologic response (SVR).MethodsThe study comprised 59 patients from two cohorts. Patients underwent paired HVPG (pretreatment and after SVR), liver stiffness (LSM), and enhanced liver fibrosis scores (ELF) measurements, as well as proteomics‐based profiling on serum samples using SomaScan® at baseline (BL) and after SVR (EOS). Machine learning with feature selection (Caret, Random Forest and RPART) methods were performed to determine the proteins capable of classifying HVPG responders. Model performance was evaluated using AUROC (pROC R package).ResultsPatients were stratified by a change in HVPG (EOS vs. BL) into responders (greater than 20% decline in HVPG from BL, or <10 mmHg at EOS with >10 mmHg at BL) and non‐responders. LSM and ELF decreased markedly after SVR but did not correlate with HVPG response. SomaScan (SomaLogic, Inc., Boulder, CO) analysis revealed a substantial shift in the peripheral proteome composition, reflected by 82 significantly differentially abundant proteins. Twelve proteins accurately distinguished responders from non‐responders, with an AUROC of .86, sensitivity of 83%, specificity of 83%, accuracy of 83%, PPV of 83%, and NPV of 83%.ConclusionsA combined non‐invasive soluble protein signature was identified, capable of accurately predicting HVPG response in HCV liver cirrhosis patients after achieving SVR.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionsupporting

confidence: 67%

Non‐invasive candidate protein signature predicts hepatic venous pressure gradient reduction in cirrhotic patients after sustained virologic response

Richards

Guo²,

Zou³

et al. 2023

Liver International

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“…Also the sGC-stimulators may find the way into the clinical practice, yet still a further validation is required (66). Urotensinreceptor antagonists show a very interesting profile, since it decreases hepatic resistance and increases splanchnic resistance, probably due to the differential effects on the receptor depending on the location (58,199,200). Janus kinase 2 (JAK2)-inhibition is a potential feasible strategy, which may have some potential interest, yet more investigation is needed, since it may aggravate steatosis, if not targeted to the HSC (201)(202)(203)(204)(205)(206).…”

Section: Single Drug Treatmentsmentioning

confidence: 99%

Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy

2021

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Bu nedenlerle ÜT 2 kalp yetersizliği, yüksek tansiyon ve preeklampsi gibi kardiyovasküler sistem hastalıklarıyla, diyabetes mellitus gibi endokrin sistem hastalıklarıyla, çeşitli böbrek ve karaciğer hastalıklarıyla ve noröpsikiyatrik hastalıklarla ilişkilendirilmiştir (14)(15)(16). Yapılan çeşitli çalışmalarda vücuttaki ÜT 2 konsantrasyonlarının kalp, karaciğer ve renal hastalıklarda, ateroskleroz ve hipertansiyon gibi kardiyovasküler hastalıklarda ve diyabetes mellitusta yükseldiği gösterilmiştir (6,(17)(18)(19)(20)(21)(22). ÜTR 2' ü, G proteinine bağlı olup 'GPR14' olarak adlandırılmıştır.…”

Section: Introductionunclassified

Prepubertal Ve Postpubertal Sıçanların Genital Sistem Organlarında Ürotensin 2 Reseptörünün Karşılaştırılması

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2020

Atatürk Üniversitesi Veteriner Bilimleri Dergisi

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Öz: Çalışmada sıçanlarda genital organlarda (over, uterus ve testis) puberte öncesi ve sonrasında Ürotensin 2 Reseptör'ü (ÜTR 2) varlığını ve dağılımını karşılaştırmalı olarak araştırmayı amaçladık. Çalışma toplam 20 adet Wistar Albino cinsi sıçan ile yapıldı. Sıçanlar 2 grup (N:5) erkek (Grup 1: prepubertal erkek, Grup 2: postpubertal erkek) ve 2 grup (N:5) dişi (Grup 3: prepubertal dişi, Grup 4: postpubertal dişi) olmak üzere 4 gruba ayrıldı. Sıçanlardan uterus, over ve testis örnekleri alındı. Moleküler çalışmada ÜTR 2 mRNA ekspresyon seviyeleri gerçek zamanlı polimeraz zincir reaksiyonu) ile incelendi ve immünohistokimyasal olarak ÜTR 2 boyaması ile sonuçlar karşılaştırıp bu dokularda ÜTR 2 varlığı ve dağılımı araştırıldı. Dişi sıçanlarda prepubertal ve postpubertal over ve uterus dokularında ÜTR 2 mRNA ekspresyon seviyeleri değerlendirildiğinde postpubertede istatiksel olarak anlamlı oranda artmış olarak bulunurken, erkek sıçanların testis dokularındaki ÜTR 2 mRNA ekspresyon seviyelerinde prepuberte ve postpubertede arasında bir fark görülmedi. Postpubertal over ve uterusta artan ÜTR 2 seviyelerinin artan östrojen ya da progesteron seviyeleri ile ilişkili olabileceği düşünüldü. Over ve uterus hastalıklarında ÜTR 2' ünün ayrıntılı olarak araştırılması ve ÜTR 2'ü agonist ve antagonistleri ile ilgili over ve uterus hastalıklarında ileri araştırmalar yapılması gerekliliği sonucuna varıldı.

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Urotensin II receptor antagonist reduces hepatic resistance and portal pressure through enhanced eNOS-dependent HSC vasodilatation in CCl4-induced cirrhotic rats

Cited by 11 publications

References 38 publications

Non‐invasive candidate protein signature predicts hepatic venous pressure gradient reduction in cirrhotic patients after sustained virologic response

Non‐invasive candidate protein signature predicts hepatic venous pressure gradient reduction in cirrhotic patients after sustained virologic response

Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy

Prepubertal Ve Postpubertal Sıçanların Genital Sistem Organlarında Ürotensin 2 Reseptörünün Karşılaştırılması

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