Galectin-3 inhibits cardiac contractility via a tumor necrosis factor alpha-dependent mechanism in cirrhotic rats

Background/aims: Galectin-3 plays a key pathogenic role in cardiac hypertrophy and heart failure. The present study aimed to investigate the effects of Galectin-3 on cardiomyopathy - related factors and cardiac contractility in a rat model of cirrhotic cardiomyopathy.

Methods: Rats were divided into two sets, one for a functional study, the Other for cardiac contractile-related protein evaluation. There were four groups in each set: sham operated and sham plus N-acetyllactosamine (N-Lac, a Galectin-3 inhibitor; 5 mg/kg); bile duct ligated (BDL) and BDL plus N-Lac. Four weeks after surgery, ventricular level of Galectin-3, Collagen I and III ratio, tumor necrosis factor alpha (TNFα), and brain natriuretic peptide (BNP) were measured either by Western blots or immunohistochemistry or enzyme-linked immunosorbent assay. Blood pressure was measured by polygraph recorder. Cardiomyocyte contractility was measured by inverted microscopy.

Results: Galectin-3 and Collagen I/III ratio were significantly increased in cirrhotic hearts. TNFα and BNP were significantly increased in BDL serum and heart compared with sham controls. Galectin-3 Inhibitor significantly decreased Galectin-3, TNFα, and BNP in cirrhotic hearts but not in sham controls. N-Lac also significantly improved the blood pressure, and systolic and diastolic cardiomyocyte contractility in cirrhotic rats but had no effect on sham controls.

Conclusion: Increased Galectin-3 in the cirrhotic heart significantly inhibited contractility via TNFα. Inhibition of Galectin-3 decreased the cardiac content of TNFα and BNP and reversed the decreased blood pressure and depressed contractility in the cirrhotic heart. Galectin-3 appears to play a pathogenic role in cirrhotic cardiomyopathy.