Premium
Nuclear factor‐κB inhibition improves myocardial contractility in rats with cirrhotic cardiomyopathy
Author(s) -
Liu Hongqun,
Lee Samuel S.
Publication year - 2008
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2008.01692.x
Subject(s) - contractility , pyrrolidine dithiocarbamate , medicine , pathogenesis , endocrinology , cardiomyopathy , cirrhosis , cytokine , tumor necrosis factor alpha , heart failure , nf κb , inflammation
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.