Could protein content of Urinary Extracellular Vesicles be useful to detect Cirrhosis in Alcoholic Liver Disease?

Abstract

Alcohol abuse has a high impact on the mortality and morbidity related to a great number of diseases and is responsible for the development of alcoholic liver disease (ALD). It remains challenging to detect and evaluate its severity, which is crucial for prognosis. In this work, we studied if urinary EVs (uEVs) could serve in diagnose and evaluate cirrhosis in ALD. To this purpose, uEVs characterization by cryo-electron microscopy (Cryo-EM), Nanoparticle Tracking Analysis (NTA) and Western blotting (WB) was performed in a cohort of 21 controls and 21 cirrhotic patients. Then, proteomics of uEVs was carried out in a second cohort of 6 controls and 8 patients in order to identify new putative biomarkers for cirrhosis in ALD. Interestingly, uEVs concentration, size and protein composition were altered in cirrhotic patients. From a total of 1304 proteins identified in uEVs, 90 of them were found to be altered in cirrhotic patients. The results suggest that uEVs could be considered as a tool and a supplier of new biomarkers for cirrhosis in ALD, whose application would be especially relevant in chronic patients. Yet, further research is necessary to obtain more relevant result in clinical terms.

Circulating Extracellular Vesicles Contain Liver-Derived RNA Species as Indicators of Severe Cholestasis-Induced Early Liver Fibrosis in Mice

“…EV size and concentration have been found to change in several liver disease settings indicating that EV-based liquid biopsy analysis can be employed for diagnostics, thus warranting further studies on the biological basis or functional relevance ( 31 ). For instance, it was shown that, in cirrhotic patients, there was an increase in size, concentration, and protein content of urinary EVs compared with controls ( 22 ). Moreover, Wetmore et al reported that the diameter of circulating EV increased in rodents after treatment with D-galactosamine, whereas Cho et al found an increased release of EV after incubation of mice and human hepatocyte cultures with acetaminophen, hence supporting our data ( 14 , 48 ).…”

Serum amyloid P component and pro-platelet basic protein in extracellular vesicles or serum are novel markers of liver fibrosis in chronic hepatitis C patients

“…Therefore, EVs are an excellent source for biomarkers. Several comprehensive analyses of EV proteins have been performed to detect liver cirrhosis biomarkers [ 31 – 33 ], but these studies have not evaluated EV protein changes due to stepwise fibrosis progression. We performed a comprehensive analysis of serum-derived EV proteins in chronic hepatitis C patients and clarified for the first time that SAP and PPBP in EVs could be markers of liver fibrosis.…”

The interaction between the major vault protein rs4788186 polymorphism, alcohol dependence, and depression among male Chinese problem drinkers

“…Alcohol consumption is a significant public health concern, leading to disabilities, poor health, and three million deaths every year. Excessive alcohol use accounts for 5.1% of the global disease burden (1). China has experienced the fastest-rising alcohol consumption in the world over the past few decades, which has been accompanied by significant increases in alcohol dependence and use disorders (2).…”