TY - JOUR
T1 - Characterization and Proteome of Circulating Extracellular Vesicles as Potential Biomarkers for NASH
AU - Povero, Davide
AU - Yamashita, Hirokazu
AU - Ren, Wenhua
AU - Subramanian, Mani G.
AU - Myers, Robert P.
AU - Eguchi, Akiko
AU - Simonetto, Douglas A.
AU - Goodman, Zachary D.
AU - Harrison, Stephen A.
AU - Sanyal, Arun J.
AU - Bosch, Jaime
AU - Feldstein, Ariel E.
N1 - Publisher Copyright:
© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Nonalcoholic fatty liver disease (NAFLD) is currently one of most common forms of chronic liver disease globally. NAFLD represents a wide spectrum of liver involvement from nonprogressive isolated steatosis to nonalcoholic steatohepatitis (NASH), characterized by liver necroinflammation and fibrosis and currently one of the top causes of end-stage liver disease and hepatocellular carcinoma. At present, there is a lack of effective treatments, and a central barrier to the development of therapies is the requirement for an invasive liver biopsy for diagnosis of NASH. Discovery of reliable, noninvasive biomarkers are urgently needed. In this study, we tested whether circulating extracellular vesicles (EVs), cell-derived small membrane-surrounded structures with a rich cargo of bioactive molecules, may serve as reliable noninvasive “liquid biopsies” for NASH diagnosis and assessment of disease severity. Total circulating EVs and hepatocyte-derived EVs were isolated by differential centrifugation and size-exclusion chromatography from serum samples of healthy individuals, patients with precirrhotic NASH, and patients with cirrhotic NASH. EVs were further characterized by flow cytometry, electron microscopy, western blotting, and dynamic light scattering assays before performing a proteomics analysis. Our findings suggest that levels of total and hepatocyte-derived EVs correlate with NASH clinical characteristics and disease severity. Additionally, using proteomics data, we developed understandable, powerful, and unique EV-based proteomic signatures for potential diagnosis of advanced NASH. Conclusion: Our study shows that the quantity and protein constituents of circulating EVs provide strong evidence for EV protein–based liquid biopsies for NAFLD/NASH diagnosis.
AB - Nonalcoholic fatty liver disease (NAFLD) is currently one of most common forms of chronic liver disease globally. NAFLD represents a wide spectrum of liver involvement from nonprogressive isolated steatosis to nonalcoholic steatohepatitis (NASH), characterized by liver necroinflammation and fibrosis and currently one of the top causes of end-stage liver disease and hepatocellular carcinoma. At present, there is a lack of effective treatments, and a central barrier to the development of therapies is the requirement for an invasive liver biopsy for diagnosis of NASH. Discovery of reliable, noninvasive biomarkers are urgently needed. In this study, we tested whether circulating extracellular vesicles (EVs), cell-derived small membrane-surrounded structures with a rich cargo of bioactive molecules, may serve as reliable noninvasive “liquid biopsies” for NASH diagnosis and assessment of disease severity. Total circulating EVs and hepatocyte-derived EVs were isolated by differential centrifugation and size-exclusion chromatography from serum samples of healthy individuals, patients with precirrhotic NASH, and patients with cirrhotic NASH. EVs were further characterized by flow cytometry, electron microscopy, western blotting, and dynamic light scattering assays before performing a proteomics analysis. Our findings suggest that levels of total and hepatocyte-derived EVs correlate with NASH clinical characteristics and disease severity. Additionally, using proteomics data, we developed understandable, powerful, and unique EV-based proteomic signatures for potential diagnosis of advanced NASH. Conclusion: Our study shows that the quantity and protein constituents of circulating EVs provide strong evidence for EV protein–based liquid biopsies for NAFLD/NASH diagnosis.
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U2 - 10.1002/hep4.1556
DO - 10.1002/hep4.1556
M3 - Article
AN - SCOPUS:85097581523
SN - 2471-254X
VL - 4
SP - 1263
EP - 1278
JO - Hepatology Communications
JF - Hepatology Communications
IS - 9
ER -