Cardiac protein abnormalities in dilated cardiomyopathy detected by two‐dimensional polyacrylamide gel electrophoresis

Abstract

The aim of the investigation was to determine whether there are specific global quantitative and qualitative changes in protein expression in heart tissue from patients with dilated cardiomyopathy (DCM) compared with ischaemic heart disease and undiseased tissue. Two-dimensional (2-D) polyacrylamide gel electrophoresis and computer analysis was used to study protein alteration in DCM biopsy material (n=28) compared with donor heart biopsy samples (n=9) and explanted hearts from individuals suffering from ischaemic heart disease (IHD; n = 21). A total of 88 proteins displayed decreased abundance in DCM versus IHD material while five proteins had elevated levels in the DCM group (p<0.01). The most prominent changes occurred in the contractile protein myosin light chain 2 and in a group of proteins identified as desmin. These changes do not appear to be artefactual degradation events occurring during sample processing. These proteins are not apparent in electrophoretic separations of vascular tissue or cultured endothelial cells, mesothelial cells or cardiac fibroblasts, which are clearly distinguishable from the 2-D protein patterns of whole heart and of isolated cardiac myocytes and do not appear to reflect variations in the cellular composition of biopsy samples. The different protein patterns observed in cardiomyopathy showed no obvious relationship with New York Heart Association (NYHA) functional class or haemodynamic parameters. The study has demonstrated significant alterations in quantitative protein expression in the DCM heart which would have serious implications for myocyte function. These changes might be explained by altered protease activity in DCM which could exacerbate contractile dysfunction in the failing heart.

Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy

“…The finding that 27% of the identified proteins belong to the different pathways of energy metabolism that directly participate in the generation of ATP (glycolysis, ß-oxidation, tricarboxylic acid cycle, oxidative phosphorylation, and creatine kinase system) ( Table 1) is consistent with the fact that the heart requires significant energy for normal cardiac function (19,30). Moreover, most of the cardiac diseases in which mechanical dysfunction development occurs are associated with a deficit in energy production, often generated by disturbances in one or more metabolic steps of the ATP production pathways (19).…”

Posttranslational Modifications of Myosin Light Chains Determine the Protein Fate

“…In most cases, 2-dimensional electrophoresis is used to separate individual proteins and their modified forms, which are then identified and further characterized/analyzed by mass spectrometry. To date, proteomics has identified changes in more than 40 proteins in heart diseases such as dilated cardiomyopathy, varying degrees of I/R injury, and heart failure (Arrell et al 2001a;Corbett et al 1998;Foster and Van Eyk 1999;Jager et al 2002;Jiang et al 2001;Schwertz et al 2002). Proteomics is an ideal approach to elucidate PTMs associated with kinase activity.…”

A better understanding of molecular mechanisms underlying human disease

“…Proteomic approaches have been extensively used in cardiovascular diseases, focusing on heart failure, especially in dilated cardiomyopathy (DCM). 2-DE was used in the 1990s to study human DCM, revealing more than 100 cardiac proteins that were altered significantly (most of them downregulated) in human DCM [229][230][231][232]. These proteins can be cytoskeletal and myofibrilar proteins, proteins associated with stress responses and proteins associated with mitochondria and energy production.…”