Correlation relationships between the levels of microRNA and mRNA involved in pathological angiogenesis in experimental liver cirrhosis

Objective. To identify the relationships between the levels of microRNA and mRNA during pathological angiogenesis under the conditions of experimental toxic liver cirrhosis.

Materials and methods. Fibrosis and liver cirrhosis were induced in male Wistar rats using a freshly prepared solution of thioacetamide over 17 weeks. The dynamics of the process were studied at 9 time points. The areas of interlobular veins and interlobular arteries were measured in micrometers. The numbers of interlobular arteries, interlobular veins, and sinusoidal capillaries were counted. The expression levels of mRNA genes Ang, Vegfa, Tweak, Fn14, Notch1, Notch2, and microRNAs-195-5p, microRNAs-664-3p, microRNAs-489-3p, microRNAs-3085, microRNAs-3558-3p in the liver were determined by real-time polymerase chain reaction.

Results. It was found that during progressive venous angiogenesis, as well as against the background of changes in the number of interlobular veins, sinusoidal capillaries, and the area of interlobular veins, the nature and strength of correlational interactions between the genes Ang, Vegfa, Tweak, Fn14, Notch1, Notch2, and microRNAs-195-5p, microRNAs-664-3p, microRNAs-489-3p, microRNAs-3085, microRNAs-3558-3p are associated with the stage of fibrosis and liver cirrhosis. Strong, moderate, and mild correlational links (p<0.01) were identified between the genes Ang, Vegfa, Tweak, Fn14, Notch1, Notch2 throughout the experiment.

Conclusion. The obtained results indicate that the studied microRNAs - microRNAs-195-5p, microRNAs-664-3p, microRNAs-489-3p, microRNAs-3085, microRNAs-3558-3p - are involved in the processes of restructuring the intrahepatic vascular bed at different stages of experimental toxic fibrosis and liver cirrhosis. The results of the study not only reveal additional mechanisms of formation of the indicated conditions but also identify the biological role of the studied microRNAs in the progression of fibrosis and liver cirrhosis as potential targets for studying pathogenesis and developing treatment methods.

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