TY - JOUR
AU1 - Eguchi, Akiko
AU2 - Koyama, Yukinori
AU3 - Wree, Alexander
AU4 - Johnson, Casey
AU5 - Nakamura, Ryota
AU6 - Povero, Davide
AU7 - Kneiber, David
AU8 - Tameda, Masahiko
AU9 - Contreras, Patricia
AU1 - Spada, Al
AU1 - Feldstein, Ariel
AB - Development of portal hypertension (PHT) is a central prognostic factor in patients with cirrhosis. Circulating microparticles (MPs) are released by hepatocytes in a caspase-dependent manner, are increased in circulation of patients with cirrhosis, and contribute to PHT via induction of impaired vasoconstrictor responses. Here, we tested the hypothesis that emricasan, a pan- caspase inhibitor, ameliorates PHT and reduction in release of MPs. We used a short-term and long-term protocol following common bile-duct ligation (BDL) in C57BL/6 mice (10 and 20 days, respectively). Mice were treated daily via intraperitoneal injection with 10 mg/kg/day of emricasan or placebo. Circulating MP levels were analyzed using flow cytometry and function via ex vivo angiogenesis assays. In contrast to BDL-placebo group, nearly all BDL-emricasan-treated mice survived after long-term BDL. Assessment of portal pressure showed a significant increase in BDL-placebo mice compared to sham-placebo mice. In contrast, BDL-emricasan mice had significantly lower levels of portal pressure compared to BDL-placebo mice. Although emricasan treatment resulted in a decrease in fibrosis, the changes did not reach statistical significance, suggesting that the effects on PHTare at least in part independent of the anti-fibrotic effects of the drug. Following short-term BDL, hepatocellular cell death as well as liver fibrosis 
TI - Emricasan, a pan-caspase inhibitor, improves survival and portal hypertension in a murine model of common bile-duct ligation
JF - Journal of Molecular Medicine
DO - 10.1007/s00109-018-1642-9
DA - 2018-05-05
UR - https://www.deepdyve.com/lp/springer-journals/emricasan-a-pan-caspase-inhibitor-improves-survival-and-portal-n1JdMapL2z
SP - 575
EP - 583
VL - 96
IS - 6
DP - DeepDyve