Dataset Information

Hepatic and Plasma Endothelin-1 in Dogs with Chronic Hepatitis.

ABSTRACT: Endothelin (ET)-1 is a 21-amino-acid peptide with potent vasoactive properties, which increases intrahepatic resistance in patients with chronic hepatitis (CH) or cirrhosis. ET-1 concentrations have not been investigated in dogs with CH.This study compared hepatic and plasma ET-1 levels in healthy dogs and in dogs with CH, and examined the relationship between the plasma ET-1 level and portal vein pressure in dogs with CH.Fourteen healthy dogs and twenty dogs with CH were used in this study.Prospective case-control study. Hepatic ET-1 mRNA expression was determined by real-time reverse transcription polymerase chain reaction, and hepatic and plasma ET-1 levels were assessed using ELISA. Splenic pulp pressure (SPP), as an indicator of portal vein pressure, was measured laparoscopically.Hepatic ET-1 mRNA levels were 3.7 times higher in dogs with CH than in healthy dogs (P = .008). The median hepatic and plasma ET-1 protein levels were significantly higher in dogs with CH than in healthy dogs (13.20 pg/mg wet liver vs. 3.42 pg/mg wet liver, P = .004, and 0.99 pg/mL vs. 0.71 pg/mL, P = .013, respectively). Moreover, there was a weak but significant correlation between plasma ET-1 level and SPP in dogs with CH (P = .036; rs = 0.53).The results indicate that ET-1 might play an important role in the pathogenesis of portal hypertension caused by CH.

SUBMITTER: Sakamoto Y

PROVIDER: S-EPMC5435058 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Hepatic and Plasma Endothelin-1 in Dogs with Chronic Hepatitis.

Sakamoto Y Y Sakai M M Watari T T

Journal of veterinary internal medicine 20170314 3

<h4>Background</h4>Endothelin (ET)-1 is a 21-amino-acid peptide with potent vasoactive properties, which increases intrahepatic resistance in patients with chronic hepatitis (CH) or cirrhosis. ET-1 concentrations have not been investigated in dogs with CH.<h4>Hypothesis/objectives</h4>This study compared hepatic and plasma ET-1 levels in healthy dogs and in dogs with CH, and examined the relationship between the plasma ET-1 level and portal vein pressure in dogs with CH.<h4>Animals</h4>Fourteen ...[more]

PMID: 28295621

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Project description:UNLABELLED:The goal of this study was to determine whether an association exists between circulating microRNA (miRNA) levels and disease progression in chronic hepatitis C (CHC), whether plasma or extracellular vesicles (EVs) were optimal for miRNA measurement and their correlation with hepatic miRNA expression, and the mechanistic plausibility of this association. We studied 130 CHC patients prospectively followed over several decades. A comprehensive miRNA profile in plasma using microarray with 2578 probe sets showed 323 miRNAs differentially expressed between healthy individuals and CHC patients, but only six that distinguished patients with mild versus severe chronic hepatitis. Eventually, let-7a/7c/7d-5p and miR-122-5p were identified as candidate predictors of disease progression. Cross-sectional analyses at the time of initial liver biopsy showed that reduced levels of let-7a/7c/7d-5p (let-7s) in plasma were correlated with advanced histological hepatic fibrosis stage and other fibrotic markers, whereas miR-122-5p levels in plasma were positively correlated with inflammatory activity, but not fibrosis. Measuring let-7s levels in EVs was not superior to intact plasma for discriminating significant hepatic fibrosis. Longitudinal analyses in 60 patients with paired liver biopsies showed that let-7s levels in plasma markedly declined over time in parallel with fibrosis progression. However, circulating let-7s levels did not parallel those in the liver. CONCLUSION:Of all miRNAs screened, the let-7 family showed the best correlation with hepatic fibrosis in CHC. A single determination of let-7s levels in plasma did not have superior predictive value for significant hepatic fibrosis compared with that of fibrosis-4 index, but the rate of let-7s decline in paired longitudinal samples correlated well with fibrosis progression. Pathway analysis suggested that low levels of let-7 may influence hepatic fibrogenesis through activation of transforming growth factor ? signaling in hepatic stellate cells. (Hepatology 2016;64:732-745).

Project description:Chronic hepatitis is the most common hepatic disease in dogs. Copper accumulation is an important cause of chronic hepatitis in dogs; however, the etiology in most dogs cannot be determined. Clinical signs of chronic hepatitis are often non-specific; therefore, this disease is frequently diagnosed in an advanced stage that makes successful intervention less likely. Early diagnosis of chronic hepatitis in dogs would thus be beneficial. The identification of proteins that are differentially expressed in dogs with chronic hepatitis could contribute to the development of novel diagnostic markers for this disease and provide insight into its pathogenesis. The objective of this study was to identify novel proteins that are differentially expressed in the liver of dogs with chronic hepatitis. Hepatic tissue was collected from 8 healthy dogs during ovariohysterectomy and from 8 dogs with histologically confirmed chronic hepatitis. The proteome of the liver samples was extracted by mechanical disruption and detergent-based cell lysis and differentially labeled prior to analysis by 2-dimensional fluorescence difference gel electrophoresis. Spots with an absolute fold change value > 2.0 were selected for further analysis. Protein identification was achieved by nanoflow liquid chromatography tandem mass spectrometry. Differential expression of select proteins was validated by Western blot. Five protein spots were differentially expressed between patients with chronic hepatitis and healthy control dogs. From these 5 protein spots 11 proteins were identified. Differential expression of cytokeratin 18 and annexin 5 were confirmed by Western blot analysis. Differential protein expression was shown between dogs with chronic hepatitis and healthy control dogs. Upregulation of cytokeratin 18 in chronic hepatitis may suggest increased hepatocellular apoptosis and necrosis, whereas upregulation of annexin 5A suggests increased hepatocellular apoptosis. Further studies are needed to determine whether either protein has diagnostic utility.

Dataset Information

Hepatic and Plasma Endothelin-1 in Dogs with Chronic Hepatitis.

Publications

Hepatic and Plasma Endothelin-1 in Dogs with Chronic Hepatitis.

Similar Datasets

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