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Expression of Desmin in the context of Desmin gene and Ubiquitin expression in patients with idiopathic dilated Cardiomyopathy

Author: 
Agnieszka Pawlak, Emilia Rejmak- Kozicka, Katarzyna Gil, Andrzej Ziemba, Leszek Kaczmarek and Gil, R. J.
Subject Area: 
Health Sciences
Abstract: 

Background: Desmin as one of the major stress-bearing elements in the sarcomere and intercalated disk is an important determinant of cardiomyocyte function and long outcome. However, DES disturbances have been noticed in various heart diseases and can be modified by DES mRNA and ubiquitin proteasome system. The relation between desmin mRNA, desmin and ubiquitin in patients with idiopathic dilated cardiomyopathy (IDCM) has not been examined. Aim: The evaluation of desmin and ubiquitin gene expression and ubiquitin expression in different types of desmin expression in cardiomyocytes in patients with IDCM. Methods: Left ventricular endomyocardial biopsy was performed in 60 patients (85% males, mean age 46±14 years) with clinical symptoms of heart failure (HF) and left ventricular ejection fraction <45%. Expression and localization of desmin and ubiquitin were analysed in histological sections by immunohistochemical method using anti-desmin and anti-ubiquitin (DAKO) antibodies. Desmin mRNA expression and localization was determined by FISH methods. Western-blott (W-b) was performed to quantify analysis of desmin and ubiquitin. Patients were assigned to four types according to the desmin expression in cardiomyocytes: type I, 9 patients with normal desmin expression; type IIA, 23 patients with high desmin expression in physiological localisation, type IIB, 20 patients with high desmin expression and desmin aggregates; group III, 8 patients with low desmin expression in cardiomyocytes. Results: In group I, even and weak expression of ubiquitin in the cytosol and low expression of desmin mRNA in cytosol and nuclei of cardiomyocytes was observed. The expression of ubiquitin and desmin mRNA increased along with the progression of desmin cytoskeleton remodeling (type IIA and IIB). Desmin mRNA and ubiquitin were weakly expressed or not present in myocardium of patients from desmin type III. The desmin mRNA, desmin and ubiquitin expression in cardiomyocyte was associated with gradual changes in cardiomyocyte structure (increase in cardiomyocytes hypertrophy and fibrosis) as well as HF progress (higher NYHA class, increase in the level of N-terminal pro-brain natriuretic protein and left ventricular end diastolic diameter and decrease in left ventricular ejection fraction). Conclusions: The ubiquitin and the mRNA of desmin can modify the level of desmin expression. Increase in expression of ubiquitin and desmin mRNA might be a feature associated with protection an unfavorable cell remodeling, which reduces the adverse effects of cytoskeleton damage in the early stage of HF. It seems that the lack of ubiquitin and low desmin mRNA expression can be a marker of the end stage HF.

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