In this research, we compared the cognitive parameters of 2-, 7-, and 15-month-old mice, changes in mitochondrial DNA (mtDNA) integrity and expression of genes involved in the nuclear erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway. We showed an age-related decrease in the Nfe2l2 expression in the cerebral cortex, not in the hippocampus. At the same time, we find an increase in the mtDNA copy number in the cerebral cortex, despite the lack of an increase in gene expression, which is involved in the mitochondrial biogenesis regulation. We suppose that increase in mtDNA content is associated with mitophagy downregulation. We supposed that mitophagy downregulation may be associated with an age-related increase in the mtDNA damage. In the hippocampus, we found a decrease in the Bdnf expression, which is involved in the pathways, which play an essential role in regulating long-term memory formation. We showed a deficit of working and reference memory in 15-month-old-mice in the water Morris maze, and a decrease in the exploratory behavior in the open field test. Cognitive impairments in 15-month-old mice correlated with a decrease in Bdnf expression in the hippocampus, Nfe2l2 expression, and an increase in the number of mtDNA damage in the cerebral cortex. Thus, these signaling pathways may be perspective targets for pharmacological intervention to maintain mitochondrial quality control, neuronal plasticity, and prevent the development of age-related cognitive impairment.

Cardiovascular diseases (CVD) and, in particular, atherosclerosis, remain the main cause of death in the world today. Unfortunately, in most cases, CVD therapy begins after the onset of clinical symptoms and is aimed at eliminating them. In this regard, early pathogenetic therapy for CVD remains an urgent problem in modern science and healthcare. Cell therapy, aimed at eliminating tissue damage underlying the pathogenesis of some pathologies, including CVD, by replacing it with various cells, is of the greatest interest. Currently, cell therapy is the most actively developed and potentially the most effective treatment strategy for CVD associated with atherosclerosis. However, this type of therapy has some limitations. In this review, we have tried to summarize the main targets of cell therapy for CVD and atherosclerosis in particular based on the analysis using the PubMed and Scopus databases up to May 2023.

Mechanical properties of living cells play a crucial role in a wide range of biological functions and pathologies, including atherosclerosis. We used low-stress Scanning Ion-Conductance Microscopy (SICM) correlated with confocal imaging and demonstrated the topographical changes and mechanical properties alterations in EA.hy926 and THP-1 exposed to LDL extracted from CVD patients’ blood samples. We show that the cells stiffened in the presence of LDL, which also triggered caveolae formation. Endothelial cells accumulated less cholesterol in the form of lipid droplets in comparison to THP-1 cells based on fluorescence intensity data and biochemical analysis; however, the effect on Young’s modulus is higher. The cell stiffness is closely connected to the distribution of lipid droplets along the z-axis. In conclusion, we show that the sensitivity of endothelial cells to LDL is higher compared to that of THP-1, triggering changes in the cytoskeleton and membrane stiffness which may result in the increased permeability of the intima layer due to loss of intercellular connections and adhesion.

Myocardial edema is the excess accumulation of fluid in the myocardial interstitium or cardiac cells that develops due to changes in capillary permeability, loss of glycocalyx charge, imbalance in lymphatic drainage, or a combination of these factors. Today it is believed that this condition is not only a complication of cardiovascular diseases, but in itself causes aggravation of the disease and increases the risks of adverse outcomes. The study of molecular, genetic, and mechanical changes in the myocardium during edema may contribute to the development of new approaches to the diagnosis and treatment of this condition. This review was conducted to describe the main mechanisms of myocardial edema development at the molecular and cellular levels and to identify promising targets for the regulation of this condition based on articles cited in Pubmed up to January 2024.

Vascular smooth muscle cells (VSMCs) are one of the main cell types that constitute the vascular wall and play an important role in the development of cardiovascular diseases (CVDs). Normally, VSMCs are primarily involved in regulating vascular tone. Under pathological conditions, their phenotypic switching from a contractile to a pathological phenotype occurs, which is accompanied by impaired contractile function. These disorders lead to the development of different CVDs. In this regard, the aim of this review was to assess the influence of the features of differentiation pathways of VSMCs from embryonic progenitor cells and various transcription factors on the development of CVDs. Primary attention is given to the mechanisms of phenotypic switching of VSMCs, which plays a key role in the pathogenesis of vascular disorders. Particular emphasis is placed on investigating the effect of microRNAs (miRs) on the functional state of VSMCs. The analysis of current data demonstrates that alterations in miR expression result in significant functional rearrangements of VSMCs, which can contribute to the progression of CVDs. Consequently, understanding the mechanisms of VSMC dysfunction presents promising opportunities for developing targeted therapies aimed at restoring normal vascular wall function and preventing the development of CVDs.

BACKGROUND: Thoracic aortic aneurysm is a chronic disease characterized by localized dilation of the vessel, including the ascending, arch and descending parts of the aorta. Aneurysm is one of the most dangerous diseases because aortic dissection or rupture can lead to sudden death. More than 150,000 people worldwide die from aortic aneurysms every year. Despite its prevalence, the cellular mechanisms of its development remain not fully understood. AIM: To evaluate phagocytic activity and proinflammatory activation capability of smooth muscle cells isolated from tunica intima and tunica media of the thoracic part of the human aorta in patients with aneurysm. MATERIALS AND METHODS: The experiments were performed on a culture of primary smooth muscle cells isolated from aneurysm patients. Linear cultures (mesenchymal stem cells ASC52telo, fibroblasts 977hTERT, THP-1, CLTH-CL05008 and EA.hy926) and smooth muscle cells isolated from healthy donors were used as controls. Phagocytic activity was assessed by introducing latex beads to the studied cells, while the ability to internalize low-density lipoprotein was evaluated using the dye BDP 630/650 (Lumiprobe, Russia) and a biochemical method. Pro- and anti-inflammatory activation capability were measured using enzyme-linked immunosorbent assay, quantifying the secretion of cytokines, namely IL-8, IL-6 and IL-10. RESULTS: The study showed that the smooth cells have high phagocytic activity and the ability to internalize low-density lipoprotein. Thus, primary smooth muscle cells from tunica media have greater phagocytic activity than smooth muscle cells obtained from healthy donors (p 0.001). In addition, IL-6 secretion after incubation with latex beads was significantly higher in smooth muscle cells from tunica media compared to those from healthy donors (p 0.001). IL-6 secretion also increased after incubation with low-density lipoprotein in smooth muscle cells from tunica intima compared to cells from healthy donors (p 0.001). CONCLUSION: The absorption of latex beads and low-density lipoprotein stimulates the secretion of proinflammatory IL-6 by primary smooth muscle cells from tunica intima and smooth muscle cells from tunica media, which are part of the aortic wall of patients with aneurysm.