Characterization of myocardial protein composition in dilated cardiomyopathy by two-dimensional gel electrophoresis.

In order to identify alterations in the myocardial protein pattern that characterize dilated cardiomyopathy (DCM), we compared, by two-dimensional gel electrophoresis, right atrial protein patterns from five patients with DCM and four with normal left ventricular function (two gels per patient). Using computer assisted analysis (PDQUEST, 4.1) we found reproducible protein patterns in the 18 gels (23 x 30 cm, pH 4-9, molecular weight 10-150 kDa). In the two gels from the same patient, 91% of proteins were identical in their position in the pattern and the relative intensities of these protein species correlated with r = 0.85. Three hundred and two +/- 50 protein species were found in several gels, 186 in all 18 gels. Seven proteins in the DCM group were decreased in their relative intensity by > 100%, six were increased by > 100%. Significant quantitative differences between DCM and control patients were found for 25 protein species. Based on seven external marker proteins, a pH and molecular weight value could be calculated for each protein. So far, 30 protein species have been identified by antibodies, amino acid analysis or sequencing procedures. From the 25 proteins that are significantly different between DCM and controls, three have been identified. Expression of the mitochondrial creatine kinase and alpha cristallin B chain was significantly increased in DCM; the malate dehydrogenase family was also significantly decreased in DCM. Two-dimensional electrophoresis appears to be a powerful method for the detection of disease-associated alterations in the myocardial protein pattern.