Cirrhotic cardiomyopathy (CCM) is a significant complication of cirrhosis, but its progression and underlying mechanisms remain incompletely understood. This study aimed to investigate dynamic changes in cardiac function, pathology, inflammation, and mitochondrial damage in a mouse model of CCM, and to compare echocardiographic characteristics in patients with cirrhosis.
Methods
Bile duct ligation was performed in male C57BL/6J mice to induce cirrhosis. Longitudinal analyses were conducted over eight weeks. Cardiac function was assessed using serum biomarkers, echocardiography, and electrocardiography. Pathology was examined with hematoxylin and eosin, Masson's trichrome, Sirius Red, and wheat germ agglutinin staining. Western blotting and immunohistochemistry were used to detect markers of inflammation, fibrosis, apoptosis, and mitochondrial function. Cardiac and liver function markers were also evaluated in patients with cirrhosis.
Results
Mice subjected to bile duct ligation developed progressive cardiac dysfunction, including reduced cardiac output and diastolic dysfunction (end-diastolic interventricular septal thickness, left ventricular internal diameters, stroke volume, and left ventricular end-diastolic volume decreased, whereas ejection fraction and fractional shortening increased), as well as cardiac atrophy. Myocardial apoptosis, inflammation (elevated tumor necrosis factor, interleukin-6, and p65), and fibrosis worsened over time. Mitochondrial injury was characterized by reduced carnitine palmitoyltransferase 1A and peroxisome proliferator-activated receptor alpha, with increased hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A. In patients with cirrhosis, impaired cardiac function and elevated brain natriuretic peptide levels correlated with total bilirubin.
Conclusions
Our results indicate that mice subjected to BDL develop progressive cardiac dysfunction, with fibrotic changes detectable as early as four weeks post-surgery. Inflammation and mitochondrial damage likely contribute significantly to this process, although the precise mechanisms require further investigation. In patients with cirrhosis, cardiac dysfunction is closely associated with disease severity, highlighting the importance of monitoring cardiac function and electrocardiograms in clinical practice. However, the EF values observed in BDL-treated mice did not align with the established diagnostic criteria for CCM in patients. This discrepancy is likely attributable to cardiac atrophy in these mice, whereas CCM in patients is typically characterized by myocardial hypertrophy and chamber dilation. Such differences should be taken into account in future mechanistic studies.
Full text
https://www.xiahepublishing.com/2310-8819/JCTH-2025-00237
The study was recently published in the Journal of Clinical and Translational Hepatology .
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