Cardiomyopathy reverses with recovery of liver injury, cholestasis and cholanemia in mouse model of biliary fibrosis
Article first published online: 12 JAN 2014
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
How to Cite
Desai, M. S., Eblimit, Z., Thevananther, S., Kosters, A., Moore, D. D., Penny, D. J. and Karpen, S. J. (2014), Cardiomyopathy reverses with recovery of liver injury, cholestasis and cholanemia in mouse model of biliary fibrosis. Liver International. doi: 10.1111/liv.12438
- Article first published online: 12 JAN 2014
- Accepted manuscript online: 14 DEC 2013 03:48AM EST
- Manuscript Accepted: 7 DEC 2013
- Manuscript Received: 28 MAY 2013
- . Grant Number: P30DK056338
- NIH. Grant Numbers: HD0473 K-12, DK58338, DK56239
- Texas Gulf Coast Digestive Disease Center
- The Cade R. Alpard Foundation
- bile acid-myocardial interaction;
- cardiac adaptation;
- hepatic – cardiopathy;
- liver injury;
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.
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.
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 analysed for key components of function and cell signalling. Cardiac physiological and molecular parameters were similarly analysed in Abcb11−/− mice (n = 5/grp) fed 0.5% cholic acid supplemented diet for 1 week.
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 physiological and molecular parameters correlated with degree of cholanemia. Cardiomyopathy was reproduced in cholanemic BA fed Abcb11−/− mice.
Cardiomyopathy resolves with resolution of liver injury, is associated with cholanaemia, and can be induced by BA feeding.