Document Detail


Cardiomyopathy reverses with recovery of liver injury, cholestasis and cholanemia in mouse model of biliary fibrosis.
MedLine Citation:
PMID:  24330504     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Triggers and exacerbants of cirrhotic cardiomyopathy (CC) are poorly understood, limiting treatment options in patients with chronic liver diseases. Liver transplantation alone reverses some features of CC, but the physiology behind this effect has never been studied.
AIMS: We aimed to determine whether reversal of liver injury and fibrosis in mouse affects cardiac parameters. The second aim was to determine whether cardiomyopathy can be induced by specifically increasing systemic bile acid (BA) levels.
METHODS: 6-8 week old male C57BL6J mice were fed either chow (n=5) or 3, 5-diethoxycarbonyl-1, 4-dihydroxychollidine (DDC) (n=10) for 3 weeks. At the end of 3 weeks, half the mice in the DDC fed group were randomized to chow (the reversed [REV] group). Serial ECHOs and electrocardiographic analysis was conducted weekly for 6 weeks followed by liver tissue and serum studies. Hearts were analyzed for key components of function and cell signaling. Cardiac physiologic and molecular parameters were similarly analyzed in Abcb11(-/-) mice (n=5/grp) fed 0.5% cholic acid supplemented diet for 1 week.
RESULTS: Mice in the REV group showed normalization of biochemical markers of liver injury with resolution of electrocardiographic and ECHO aberrations. Catecholamine resistance seen in DDC group resolved in the REV group. Cardiac recovery was accompanied by normalization of cardiac troponin-T2 as well as resolution of cardiac stress response at RNA level. Cardiovascular physiologic and molecular parameters correlated with degree of cholanemia. Cardiomyopathy was reproduced in cholanemic BA fed Abcb11(-/-) mice.
CONCLUSIONS: Cardiomyopathy resolves with resolution of liver injury, is associated with cholanemia, and can be induced by BA feeding. This article is protected by copyright. All rights reserved.
Authors:
Moreshwar S Desai; Zeena Eblimit; Sundararajah Thevananther; Astrid Kosters; David D Moore; Daniel J Penny; Saul J Karpen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-14
Journal Detail:
Title:  Liver international : official journal of the International Association for the Study of the Liver     Volume:  -     ISSN:  1478-3231     ISO Abbreviation:  Liver Int.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101160857     Medline TA:  Liver Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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