{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:50:52Z","timestamp":1790128252922,"version":"4.0.1"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T00:00:00Z","timestamp":1562716800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:p>Circulating extracellular vesicles (EVs) are a novel and emerging biomarker for nonalcoholic steatohepatitis (NASH). It has been demonstrated that total circulating EVs and hepatocyte\u2010derived EVs are elevated in male mice with diet\u2010induced NASH. How hepatocyte\u2010derived EVs change over time and other cellular sources of EVs in NASH have not been determined. Our objective was to define the quantitative evolution of hepatocyte\u2010derived, macrophage\u2010derived, neutrophil\u2010derived, and platelet\u2010derived EVs in male and female mice with dietary NASH. Fluorescently labeled antibodies and a nanoscale flow cytometer were used to detect plasma levels of EVs. Asialoglycoprotein receptor 1 (ASGR1) and cytochrome P450 family 2 subfamily E member 1 (CYP2E1) are markers of hepatocyte\u2010derived EVs; galectin 3 is a marker of macrophage\u2010derived EVs; common epitope on lymphocyte antigen 6 complex, locus G\/C1 (Ly\u20106G and Ly\u20106C) is a marker of neutrophil\u2010derived EVs; and clusters of differentiation 61 (CD61) is a marker of platelet\u2010derived EVs. Nonalcoholic fatty liver disease activity score (NAS) was calculated using hematoxylin and eosin\u2010stained liver sections, and magnetic resonance imaging (MRI) was used for measurement of the fat fraction and elastography. Hepatocyte\u2010derived EVs increased in both male and female mice at 12 and 10 weeks of feeding, respectively, and remained elevated at 24 weeks in both male and female mice and at 48 weeks in male mice and 36 weeks in female mice. Macrophage\u2010 and neutrophil\u2010derived EVs were significantly elevated at 24 weeks of dietary feeding concomitant with the histologic presence of inflammatory foci in the liver. In fat\u2010, fructose\u2010, and cholesterol\u2010 (FFC) fed male mice, platelet\u2010derived EVs were elevated at 12, 24, and 48 weeks, whereas in female mice, platelet derived EVs were significantly elevated at 24 weeks. Hepatocyte\u2010, macrophage\u2010 and neutrophil\u2010derived EVs correlated well with the histologic NAS. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Circulating cell\u2010type\u2010specific EVs may be a novel biomarker for NASH diagnosis and longitudinal follow up.<\/jats:p>","DOI":"10.1002\/hep4.1404","type":"journal-article","created":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T18:04:35Z","timestamp":1562781875000},"page":"1235-1249","source":"Crossref","is-referenced-by-count":60,"title":["Characterization of Cellular Sources and Circulating Levels of Extracellular Vesicles in a Dietary Murine Model of Nonalcoholic Steatohepatitis"],"prefix":"10.1097","volume":"3","author":[{"given":"Jiahui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Radiology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"},{"name":"Center of Integrative Medicine,Beijing Ditan Hospital Capital Medical University,Beijing,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S.","family":"Mauer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Lucien","sequence":"additional","affiliation":[{"name":"Department of Urology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abagail","family":"Raiter","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harikrishna","family":"Bandla","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taofic","family":"Mounajjed","sequence":"additional","affiliation":[{"name":"Division of Anatomic Pathology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziying","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Radiology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Glaser","sequence":"additional","affiliation":[{"name":"Department of Radiology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Radiology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harmeet","family":"Malhi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,7,10]]},"reference":[{"key":"hep41404-bib-0001-20240114","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention","volume":"15","year":"2018","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"hep41404-bib-0002-20240114","first-page":"pii:95354","article-title":"Therapeutic opportunities for alcoholic steatohepatitis and nonalcoholic steatohepatitis: exploiting similarities and differences in pathogenesis. 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