Myocardial Dysfunction in Cirrhotic Cardiomyopathy is Associated with Alterations of Phospholamban Phosphorylation and IL-6 Levels

• Autor(a) principal: Gregolin, Cristina Schmitt
• Data de Publicação: 2021
• Outros Autores: Nascimento, Milena do, Borges de Souza, Sergio Luiz [UNESP], Ferreira Mota, Gustavo Augusto [UNESP], Bomfim, Gisele Facholi, Melo Luvizotto, Renata de Azevedo, Sugizaki, Mario Mateus, Zanati Bazan, Silmeia Garcia [UNESP], Salome de Campos, Dijon Henrique [UNESP], Dias, Marcos Correa, Correa, Camila Renata [UNESP], Cicogna, Antonio Carlos [UNESP], Nascimento, Andre Ferreira do
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• DOI: 10.1016/j.arcmed.2020.11.004
• Texto Completo: http://dx.doi.org/10.1016/j.arcmed.2020.11.004; http://hdl.handle.net/11449/210238
• topic: Cirrhotic cardiomyopathy; Cardiac dysfunction; Thioacetamide; Liver cirrhosis; Papillary muscle

Background. Decreased cardiac contractility has been observed in cirrhosis, but the mechanisms that initiate and maintain cardiac dysfunction are not entirely understood. Aim of the study. We test the hypothesis that cirrhotic cardiomyopathy is related to deterioration of myocardial contractility due to alterations in calcium-handling proteins expression. In addition, we evaluated whether cardiac pro-inflammatory cytokine levels are associated with this process. Methods. Cirrhosis was induced by thioacetamide (TAA, 100 mg/kg/i.p., twice weekly for eight weeks). The myocardial performance was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic challenge. The cardiac calcium handling protein expression was detected by Western blotting. Cardiac TNF-alpha and IL-6 levels were measured by ELISA. Results. Thioacetamide induced liver cirrhosis, which was associated with cirrhotic cardiomyopathy characterized by in vivo left ventricular diastolic and systolic dysfunction as well as cardiac hypertrophy. In vitro baseline myocardial contractility was lower in cirrhosis. Also, myocardial responsiveness to post-rest contraction stimulus was declined. Protein expression for RYR2, SERCA2, NCX, pPBL Ser16 and L-type calcium channel was quantitatively unchanged; however, pPBL Thr17 was significantly lower while IL-6 was higher. Conclusions. Our study demonstrates that cirrhotic cardiomyopathy is associated with decreased cardiac contractility with alteration of phospholamban phosphorylation in association with higher cardiac pro-inflammatory IL-6 levels. These findings provided molecular and functional insights about the effects of liver cirrhosis on cardiac function. (C) 2020 IMSS. Published by Elsevier Inc.