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Updated: Jul 6, 2026
LAD-Ligation: A Murine Model of Myocardial Infarction
Published on: October 14, 2009
Nuclear factor-kappaB inhibition improves myocardial contractility in rats with cirrhotic cardiomyopathy
1Liver Unit, University of Calgary, Calgary, AB, Canada.
Insights
Nuclear factor-kappaB (NF-kappaB) inhibition improved cardiac function in cirrhotic rats. Blocking NF-kappaB reduced tumor necrosis factor-alpha (TNF-alpha) and restored cardiomyocyte contractility, suggesting NF-kappaB
Area of Science:
- Cardiovascular Biology
- Hepatology
- Molecular Medicine
Background:
- Cirrhotic cardiomyopathy is linked to cytokines like tumor necrosis factor-alpha (TNF-alpha).
- Nuclear factor-kappaB (NF-kappaB) plays a key role in regulating cytokines and cardiac dysfunction.
- The specific role of NF-kappaB in cirrhotic cardiomyopathy requires elucidation.
Purpose of the Study:
- To investigate the involvement of NF-kappaB in the pathogenesis of cirrhotic cardiomyopathy.
- To determine if inhibiting NF-kappaB can ameliorate cardiac dysfunction in cirrhosis.
Main Methods:
- Cirrhosis was induced in rats via bile duct ligation (BDL); control rats underwent sham operations.
- NF-kappaB inhibitors (pyrrolidine dithiocarbamate and Bay 11-7082) were administered.
- Myocardial NF-kappaB and TNF-alpha expression, and cardiomyocyte contractility were assessed.
Main Results:
- Bile duct ligation led to increased myocardial NF-kappaB and TNF-alpha levels.
- NF-kappaB inhibition significantly reduced NF-kappaB activity and TNF-alpha expression in cirrhotic hearts.
- Inhibition of NF-kappaB restored contractile function in cirrhotic cardiomyocytes.
Conclusions:
- Increased NF-kappaB activity in cirrhotic hearts is associated with impaired cardiomyocyte contractility.
- NF-kappaB, potentially through cytokine modulation, contributes to the development of cirrhotic cardiomyopathy.
- Targeting NF-kappaB may offer a therapeutic strategy for cirrhotic cardiomyopathy.
Background/Aims:
Cytokines such as tumour necrosis factor (TNF-alpha) contribute to the pathogenesis of cirrhotic cardiomyopathy. Nuclear factor-kappaB (NF-kappaB) is crucial for cytokine regulation, and induces cardiac dysfunction in several heart disease models. We aimed to elucidate possible NF-kappaB 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-kappaB 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-kappaB and TNF-alpha expression was measured by Western blot and ELISA. The contractility of isolated cardiomyocytes was observed under direct microscopy.
Results:
Nuclear factor-kappaB and TNF-alpha levels were increased in cirrhotic hearts compared with controls. PDTC significantly reduced NF-kappaB activity and TNF-alpha 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-kappaB activity in cirrhotic hearts was associated with improvement of attenuated cardiomyocyte contractility. NF-kappaB, via effects on cytokine expression, may contribute to the pathogenesis of cirrhotic cardiomyopathy.
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