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Characterization and Proteome of Circulating Extracellular Vesicles as Potential Biomarkers for NASH

Povero, Davide ; Yamashita, Hirokazu ; Ren, Wenhua ; Subramanian, Mani G. ; Myers, Robert P. ; Eguchi, Akiko ; Simonetto, Douglas A. ; Goodman, Zachary D. ; Harrison, Stephen A. ; Sanyal, Arun J. ; Bosch, Jaime ; Feldstein, Ariel E.

Hepatology communications, 2020-09, Vol.4 (9), p.1263-1278 [Periódico revisado por pares]

New York: Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins

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  • Título:
    Characterization and Proteome of Circulating Extracellular Vesicles as Potential Biomarkers for NASH
  • Autor: Povero, Davide ; Yamashita, Hirokazu ; Ren, Wenhua ; Subramanian, Mani G. ; Myers, Robert P. ; Eguchi, Akiko ; Simonetto, Douglas A. ; Goodman, Zachary D. ; Harrison, Stephen A. ; Sanyal, Arun J. ; Bosch, Jaime ; Feldstein, Ariel E.
  • Assuntos: Biomarkers ; Biopsy ; Cell adhesion & migration ; Chromatography ; Extracellular vesicles ; Histology ; Kinases ; Liver cancer ; Liver diseases ; Original ; Proteins ; Proteomics ; Statistical analysis ; Transmission electron microscopy ; Validation studies
  • É parte de: Hepatology communications, 2020-09, Vol.4 (9), p.1263-1278
  • Notas: Potential conflict of interest: Dr. Subramanian owns stock in Gilead. Dr. Sanyal consults and received grants from Conatus, Gilead, Echosens‐Sandhill, malinckrodt, Salix, Novartis, Galectin, and Sequana. He consults and owns stock in GenFit, Hemoshear, Durect, and Indalo. He consults for Immuron, Intercept, Pfizer, Boehringer Ingelheim, Nimbus, Lilly, Merck, Novo Nordisk, Fractyl, Allergan, Chemomab, Affimmune, Teva, Aredlyx, Terns, ENYO, Birdrock, Albireo, Sanofi, Takeda, Janssen, Zydus, BASF, AMRA, Perspectum, Owl, Poxel, Servier, Second Genome, General Electric, and 89 Bio. He received grants from Bristol‐Myers Squibb. He received royalties from Elsevier and Uptodate. He owns stock in Exhalenz, Akarna, and Tiziana. He is employed by Sanyal Bio. Dr. Bosch consults for Gilead. Dr. Myers is employed by and owns stock in Gilead. Dr. Harrison owns stock, consults for, advises, and received grants from Cirius, Galectin, Genfit, Madrigal, Metacrine, NGM Bio, and North Sea. He owns stock in, consults for, and advises Akero and HistoIndex. He consults for, advises, and received grants from Axcella, CiVi Biopharma, CymaBay, Galmed, Gilead, HighTide, Hepion, Intercept, Novartis, Novo Nordisk, Sagimet, and Viking. He consults for and advises Altimmune, Blade Therapeutics, CLDF, Echosens, Forsite Labs, Gelesis, Indalo, Innovate, Medpace, Perspectum, Poxel, Prometic, Ridgeline Therapeutics, and Terns. He received grants from Axcella, BMS, Conatus, Enyo, Genetech, Immuron, Pfizer, Second Genome, Tobira, and Allergan.
    Supported by Gilead Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK113592).
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  • Descrição: 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. Circulating liver‐derived extracellular vesicles (EVs) are released in patients with advanced nonalcoholic steatohepatitis (NASH) and correlate with disease outcomes. Analysis of EV protein cargo identified potential multiprotein signatures that can be used as noninvasive biomarkers as an alternative to costly and invasive liver biopsy.
  • Editor: New York: Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
  • Idioma: Inglês
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