Open AccessTherapeutic Targeting of Myeloperoxidase Attenuates NASH in Mice
Author(s) -
Koop Anja Christina,
Thiele Nina Doreen,
Steins David,
Michaëlsson Erik,
Wehmeyer Malte,
Scheja Ludger,
Steglich Babett,
Huber Samuel,
Schulze zur Wiesch Julian,
Lohse Ansgar W.,
Heeren Jörg,
Kluwe Johannes
Publication year - 2020
Publication title -
hepatology communications
Language(s) - English
Resource type - Journals
ISSN - 2471-254X
DOI - 10.1002/hep4.1566
Subject(s) - myeloperoxidase , steatosis , nonalcoholic fatty liver disease , fibrosis , medicine , liver injury , steatohepatitis , hepatic fibrosis , endocrinology , fatty liver , inflammation , disease
Our study shows that in patients, systemic levels of the neutrophil enzyme myeloperoxidase (MPO) correlate with the presence of nonalcoholic steatohepatitis (NASH) and hepatic MPO expression with risk factors of NASH. Using various mouse models, we demonstrate that MPO is essential for NASH progression and consecutive liver fibrosis but not for steatosis‐independent liver fibrogenesis. In mice treated with an MPO inhibitor, AZM198, we show that MPO inhibition has the potential to attenuate NASH‐induced liver injury and fibrosis, and, moreover, is associated with beneficial changes of intestinal microbiota.