Background: Metabolic and structural changes in cardiomyocytes in diabetes mellitus lead to aggravation of contractile myocardial dysfunction in coronary heart disease (CHD). The contractility dysfunction of cardiomyocytes is determined by a change in the levels of sarcoplasmic reticulum (SR) Ca2+-ATPase and energetic supply of the cardiomyocytes. Aims: To study the features of functional remodeling of the heart muscle in coronary heart disease with and without type 2 diabetes mellitus (DM2) depend on the level of Ca2+-ATPase and the activity of enzymes involved in energy metabolism. Materials and methods: The work was performed on the heart biopsy of patients with CHD and patients with CHD combined with DM2. The inotropic reaction of myocardial strips on rest periods was assessed. The expression level of Ca2+-ATPase, the activity of enzymes succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) and the intensity of oxidative phosphorylation processes were determined. Results: The interval-force relationship in patients with CHD with and without DM2 had both negative and positive dynamics. The positive dynamics corresponds to the "high content" of the Ca2+-ATPase and the negative dynamics corresponds to the "low content" were found. At the combined pathology the positive inotropic dynamics is more pronounced and corresponds to a higher protein level. In the patients myocardium with CHD the activity of SDH and LDH was higher, while the oxygen uptake rate by mitochondria was higher in the myocardium with combined pathology. Conclusions: The potentiation of inotropic response of patient myocardium with CHD with and without DM2 corresponds to the "high level" of Ca2+-ATPase. In the combined pathology the inotropic capabilities of the myocardium are more expressed. In CHD the synthesis of ATP in cardiomyocytes is realized mainly due to glycolytic processes and Krebs cycle. In combined pathology the ATP synthesis is realized to a greater extent due to the oxidative phosphorylation.

This review contains data reflecting the role of polymorphisms and mutations of the genes of proteins Ca2+-ATPase 2a, ryanodine receptors, and calsequestrin of the Ca2+-transporting system of the...

Aim. To study the association between polymorphic rs1860561 variants of Ca(2+)-ATPase SERCA2a (ATP2A2) gene and rs3766871 of ryanodine receptor (RYR2) gene and the severity of chronic heart failure (CHF).Material and methods. We determined rs1860561 and rs3766871 variants of the ATP2A2 and RYR2 genes, respectively, in 168 patients with coronary artery disease (CAD) and CHF using real-time polymerase chain reaction.Results. A statistically significant (p=0,046) decrease in the left ventricular ejection fraction in AA homozygotes of the ATP2A2 gene compared to carriers of the G allele was shown. But among GG homozygotes, patients with FC II CHF prevailed and participants with FC I CHF were less common than among patients with genotype GA (p=0,041).Conclusion. The association of the AA genotype carriage for the rs1860561 variant of the ATP2A2 gene encoding Ca(2+)-ATPase SERCA2a, with a decrease in the left ventricle ejection fraction in patients with CHF and CAD was revealed. At the same time, among the GG homozygotes, FC I CHF was the least prevalent. There was no association of the rY3766871 variant of the RYR2 gene with CHF severity.

Сопряженность уровня гликемии и функциональных показателей миокарда у больных ишемической болезнью сердца на фоне сахарного диабета 2-го типа

BACKGROUND: Adequate glycemic control can significantly reduce the risk of developing cardiovascular events. However, until now, glycaemic targets in aged patients remain a subject of discussion, especially in the conditions of the combined development of Type 2 Diabetes Mellitus (T2DM) and ischemic heart disease (IHD).AIMS: To examine the structural and functional heart parameters in patients with IHD associated with T2DM and the rhythmoinotropic responses of their isolated myocardium depending on glycated hemoglobin level.MATERIALS AND METHODS: The study included 44 patients with a diagnosis of "chronic IHD associated with T2DM", of which 2 groups were formed. Patients with glycated hemoglobin level (HbA_1c) <8% were included in the 1^st group, and patients with HbA_1c ≥8% were included in the 2^nd group. The structural and functional heart parameters obtained with ultrasonography, and the rhythmoinotropic responses of myocardium in patients ex vivo were analyzed using the right atrial appendage fragments obtained during elective coronary artery bypass graft. The inotropic response of muscle strips at a basic stimulation frequency of 0,5 Hz to testing influences was assessed. An extrasystolic test and post-rest test were performed.RESULTS: It was found that extrasystolic contractions of isolated myocardial strips in patients of the 2^nd group appeared at shorter extrasystolic intervals, which indicates a greater excitability of the myocardium in patients of this group. Postextrasystolic muscle contractions in patients of the 2^nd group had significant potentiation. The amplitude of the muscle strips contractions in patients of both groups was potentiative after short rest periods. However, with an increase in the rest duration, potentiation of contractions was observed only in the group with a higher HbA_1c level. According to the ultrasonography data, it was found that the values of the endsystolic and diastolic volumes, the interventricular septum thickness and the left ventricular (LV) myocardium mass were significantly lower in the patients of the 1^st group compared with the corresponding indicators in the patients of the 2^nd group. The early LV filling velocity (peak E) was significantly lower in the patients of the 1^st group, which indicates a slower LV relaxation. At the same time, the rapid LV filling velocity did not have a significant intergroup difference, but this indicator exceeded the reference values in both groups.CONCLUSIONS: With a moderately increased glycemic level (9,2 [8,0; 10,3]%), the structural and functional heart parameters are preserved both at the level of the isolated myocardial tissue and at the level of the whole heart.

Background. Type 1 diabetes mellitus refers to one of the most prevalent chronic diseases. In recent years, a steady growth in this nosology has been registered in the Russian Federation, as well as globally, particularly among children and adolescents. Consequently, the number of children and adolescents classified as disabled by type 1 diabetes mellitus is also rising, prompting the global medical community to focus on mitigating these issues. The primary treatment for type 1 diabetes mellitus involves insulin replacement therapy combined with self-monitoring of blood glucose levels. Currently, insulin pumps and devices for continuous glucose monitoring have been developed and implemented in clinical practice, enhancing the effectiveness of type 1 diabetes mellitus treatment and significantly improving the quality and expectation of lives. However, even hybrid closed-loop systems (a combination of continuous subcutaneous insulin infusion and continuous glucose monitoring) fail to achieve physiological regulation of blood glucose levels and to completely eliminate the risk of long-term complications.Objectives. To explore the history of alternative preventive therapeutic methods for type 1 diabetes mellitus based on data from both Russian and international research literature.Methods. A comparative analysis of literature from both Russian and international authors addressing the issues of therapy and prevention of type 1 diabetes mellitus was conducted using the scientometric database eLibrary. ru and the biomedical search engine PubMed.Results. The search for alternative therapeutic methods that can prevent or delay the onset of the diabetes remains relevant. These therapeutic methods can be conditionally divided into conservative and surgical approaches, primarily aimed at protecting pancreatic β-cells from immune-mediated destruction. Notable immunotherapeutic agents include antiproliferative agents, systemic immunomodulators, T-cell inhibitors, monoclonal antibodies, autoantigens, various types of stem cells, dendritic cells, and microbiota therapy.Conclusion. The paper presents several experimental methods of preventive therapy for type 1 diabetes mellitus and the results of studies conducted in this area, describes the proposed mechanisms for establishing immunological tolerance. A brief overview of completed and ongoing clinical trials is provided.