Proteomic Differences in Patients with Type 2 Diabetes Mellitus and Chronic Cardiac Insufficiency with Preserved and Reduced Ejection Fraction

The search for protein markers of chronic cardiac insufficiency in combination with type 2 diabetes mellitus is an urgent task. The purpose of the study was to determine the phenotype of patients with chronic cardiac insufficiency with preserved or low ejection fraction, including those burdened with type 2 diabetes mellitus, based on the study of the protein blood profile using polyacrylamide gel electrophoresis, densitometry and mass spectrometric identification of proteins. Material and methods. In 48 patients (69.1±3.1 years) with chronic cardiac insufficiency with preserved or low ejection fraction with or without type 2 diabetes mellitus and healthy volunteers, the proteome was examined by various methods (isolation of exosomes by ultracentrifugation followed by the analysis of the serum exosomes' proteome; analysis of tryptic low molecular weight fragments of whole sera of patients by semi-quantitative MALDI mass spectrometry in the presence of an isotopically labelled standard; electrophoretic separation of serum components in polyacrylamide gel followed by densitometry; serum analysis by HPLC-MS/MS methods) in order to determine specific proteins responsible for the development of chronic cardiac insufficiency in patients with type 2 diabetes mellitus. Research results. Our study revealed the presence of inflammatory proteins (fibrinogen beta, haptoglobin, serotransferrin) and liver tissue (alpha-1-antitrypsin, ApoV) in the studied groups, some of which were reduced compared with the control group (ApoV, fibrinogen beta, serotransferrin, alpha-1-antitrypsin) against the background of standard therapy. HPLC-MS/MS using timsTOF Pro demonstrated more promising results. The differences between the comparison groups obtained using the "gel-based" approach (gel electrophoresis in polyacrylamide gel followed by densitometry) were shown for a number of other proteins (compared with the "gel-free" approach, implying only HPLC-MS/MS, without using separation in gel), which can also be explained by limitation of each of the methods: these approaches to the study of the proteome are complementary rather than interchangeable. Conclusions.There are variations in circulating proteins in patients with cardiac insufficiency associated with differences in the pathophysiology of chronic cardiac insufficiency, which are not fully fixed by the current classification based on determining the ejection fraction. High-performance proteomic analysis methods make it possible to more accurately determine the criteria for the phenotypes of chronic cardiac insufficiency with a preserved ejection fraction and, accordingly, the mechanisms of forming the pathogenetic pathways of this condition.