Cardiac arrhythmias are common disorders that can be fatal. Modern methods of treating bradyarrhythmias include the implantation of pacemakers and cardioverter–defibrillators. However, implantable devices can cause various complications related to the electrodes installed inside the heart, including infection. Less invasive heart rhythm modulation could be beneficial for some cohorts of patients. Here, we demonstrate an alternative approach to heart pacing based on thermogenetics. We used adeno-associated viruses to deliver genetic human transient receptor potential subfamily V member 1 (TRPV1), a heat-sensitive cation channel, into isolated cardiomyocytes and the mouse heart. This allowed us to induce action potentials and control contractility using short heat pulses delivered by infrared laser illumination. Using this approach, we demonstrated the thermogenetic pacing of isolated cardiomyocytes in vitro and in the mouse heart in vivo . Our results demonstrate the potential of thermogenetics for developing therapeutic strategies for heart rhythm modulation.

This review critically examines the evolving landscape of genetic animal models for investigating cardiovascular diseases (CVDs). We analyze established models, including spontaneously hypertensive rats, Watanabe hyperlipidemic rabbits, etc., and transgenic models that have advanced our understanding of essential and secondary hypertension, atherosclerosis, and non-ischemic diseases of the heart. This review systematically evaluates the translational strengths and physiological limitations of these approaches across species barriers. Particular attention is paid to emerging technologies—AAV-mediated gene delivery, CRISPR-Cas9 editing, and chemogenetic tools—that enable unprecedented precision in manipulating cardiac-specific gene expression to study pathophysiological mechanisms. We address persistent challenges including off-target effects and transgene expression variability, while highlighting innovations in synthetic vectors and tissue-specific targeting strategies. This synthesis underscores how evolving genetic technologies are revolutionizing cardiovascular research paradigms, offering refined disease models and optimized therapeutic interventions that pave the way toward personalized medicine approaches for the world’s leading cause of mortality.

Mitochondria serve as an essential component in the maintenance of cardiac function, and targeting them may represent a promising approach to handling heart failure (HF). HF in this review refers to various etiologies, including ischemic cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy, unless otherwise specified. Mitochondrial dysfunction, a distinctive feature of HF, leads to a progressive decrease in bioenergetic reserves due to switching of energy production from oxidation of fatty acids in mitochondria to glycolytic pathways. The main problem in developing methods to improve mitochondrial function lies in the fact that protein preparations injected through the bloodstream cannot enter cells through the plasma membrane. Modern gene therapy involving the delivery of missing genes to cells using adeno-associated virus (AAV) vectors has the potential to improve the function of cardiomyocytes (CMCs). This type of therapy aims to target proteins that have been lost, damaged, or altered due to pathological conditions in the myocardium. This review summarizes pathophysiological mechanisms associated with mitochondrial dysfunction, which is mainly caused by increased oxidative stress and impaired mitochondrial biodynamics under HF progression. It also addresses possible ways to modulate these processes using gene therapy. Special attention is paid to modern characteristics of AAVs that can be used as vectors for the efficient delivery of desired genes to CMCs.

Background. Currently, pseudotuberculosis is characterized by a high incidence in children and it is the second acute intestinal infection by frequency after shigellosis. The search for relationships between early changes in cell metabolism, dysfunctions of some organs and body systems under the pathogenic effect of an infectious agent and the severity, the occurrence of a non-smooth course of pseudotuberculosis in children is relevant. Aim. Search for biochemical markers to predict the severity and occurrence of a non-smooth variant of the course of pseudotuberculosis in children. Material and methods. A prospective study was performed in 125 patients with pseudotuberculosis during periods of the disease height, early convalescence and recovery: 17 patients with mild severity and a smooth course of the disease; 64 with moderate severity and smooth course of the disease; 28 with moderate severity and non-smooth course, 16 with high severity and non-smooth course of the disease. The comparison group consisted of 45 children from the IIA health group. The distribution of the examined children by sex was equal, the age ranged from 9 to 13 years. The spectrophotometric method determined the following: in blood plasma the content of malondialdehyde; in erythrocytes the concentration of reduced glutathione, the activity of glutathione reductase, glutathione peroxidase, glutathione-S-transferase and catalase. The following ratios were calculated: reduced glutathione/malondialdehyde, reduced glutathione/glutathione reductase, reduced glutathione/glutathione peroxidase, reduced glutathione/glutathione S-transferase, glutathione peroxidase/catalase. Normality of the obtained data distribution was checked using the ShapiroWilk test, and the statistical hypotheses about the difference between the studied groups were checked using the nonparametric MannWhitney test at a significance level of p 0.05. Results. In the acute period of the disease, based on the analysis, a statistically significant decrease in the ratios of reduced glutathione/malonic dialdehyde, reduced glutathione/glutathione reductase, reduced glutathione/glutathione peroxidase by 3.0, 3.5 and 3.1 times, respectively, was established (p 0.05) in patients with mild severity and smooth course; 5.3, 5.1 and 3.8 times (p 0.05) with moderate severity and smooth course; 5.8, 4.0 and 3.0 times (p 0.05) with moderate severity and non-smooth course; by 8.1 and 6.1 times (p 0.05) with heavy severity and non-smooth course relative to control values. However, during the period of early convalescence of a non-smooth course, these indicators significantly decreased by 2.2, 4.4 and 1.8 times (p 0.05) in patients with moderate severity and by 3.4, 6.8 and 2.2 times ( p 0.05) with heavy severity relative to control values. Conclusion. Prognostically significant criteria for an increase in the severity and occurrence of a non-smooth course of pseudotuberculosis in children in the acute period of the disease are a decrease in the ratios of reduced glutathione/malonic dialdehyde less than 17.0, reduced glutathione/glutathione reductase below 38.0 and reduced glutathione/glutathione peroxidase less than 12.0.

Пациенты с благоприятным и неблагоприятным исходами кардиохирургической реваскуляризации: морфологические и морфометрические характеристики миокарда