Nuclear factor-κB inhibition improves myocardial contractility in rats with cirrhotic cardiomyopathy
Article first published online: 13 MAR 2008
© 2008 The Authors
Volume 28, Issue 5, pages 640–648, May 2008
How to Cite
Liu, H. and Lee, S. S. (2008), Nuclear factor-κB inhibition improves myocardial contractility in rats with cirrhotic cardiomyopathy. Liver International, 28: 640–648. doi: 10.1111/j.1478-3231.2008.01692.x
- Issue published online: 13 MAR 2008
- Article first published online: 13 MAR 2008
- Received 17 December 2007Accepted 19 December 2007
- cell shortening;
Background/Aims: Cytokines such as tumour necrosis factor (TNF-α) contribute to the pathogenesis of cirrhotic cardiomyopathy. Nuclear factor-κB (NF-κB) is crucial for cytokine regulation, and induces cardiac dysfunction in several heart disease models. We aimed to elucidate possible NF-κB involvement in cirrhotic cardiomyopathy.
Methods: Rats were bile duct ligated (BDL) to produce cirrhosis; controls received sham operation. Animals were studied 4 weeks later. Two NF-κB inhibitors were used: pyrrolidine dithiocarbamate (PDTC) and Bay 11-7082. Four groups were studied in most protocols: sham control, sham+PDTC, BDL and BDL+PDTC. Additional contractility studies were performed with Bay 11-7082. Myocardial NF-κB and TNF-α expression was measured by Western blot and ELISA. The contractility of isolated cardiomyocytes was observed under direct microscopy.
Results: Nuclear factor-κB and TNF-α levels were increased in cirrhotic hearts compared with controls. PDTC significantly reduced NF-κB activity and TNF-α expression in cirrhotic hearts; controls were unaffected. Cirrhotic cardiomyocytes showed decreased systolic and diatolic velocity compared with sham controls. Both PDTC and Bay 11-7082 restored contractile function in cirrhotic cardiomyocytes, but did not affect controls.
Conclusions: Inhibition of the increased NF-κB activity in cirrhotic hearts was associated with improvement of attenuated cardiomyocyte contractility. NF-κB, via effects on cytokine expression, may contribute to the pathogenesis of cirrhotic cardiomyopathy.