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.

Introduction: Systemic scleroderma (SSc) is a chronic autoimmune disease of inflammatory origin. Mitochondrial dysfunction is considered as an important mechanism in the pathogenesis of SSc. Currently mitochondrial DNA (mtDNA) copy number is used as a surrogate marker of mitochondrial dysfunction. Previous studies demonstrate that innate immune cells are important participants in inflammatory and fibrotic processes in SSc. The aim of the study was to evaluate the number of mtDNA copies in CD14⁺ monocytes and whole blood of patients with SSc in comparison with healthy individuals.Methods: Absolute mtDNA copy number was measured using digital PCR. It was found that the number of mtDNA copies in CD14⁺ monocytes was significantly higher in patients with SSc compared to control, while the number of mtDNA copies in the whole blood did not have significant differences.Results: The correlation analysis revealed an inverse association of mtDNA copy number with disease duration and the relationship between pro-inflammatory activation of CD14⁺ monocytes in terms of LPS-stimulated IL-6 secretion and mtDNA copy number. At the same time, basal and LPS-stimulated secretion of IL-6 by cultured CD+ monocytes were significantly higher in SSc group in comparison with control.Discussion: The study results suggest that increase of mtDNA copy number in CD14⁺ monocytes is a possible mechanism to maintain the reduced function of defective mitochondria in monocytes from patients with SSc associated with the development and progression of SSc.

Myocardial edema is a common symptom of pathological processes in the heart, causing aggravation of cardiovascular diseases and leading to irreversible myocardial remodeling. Patient-based studies show that myocardial edema is associated with arrhythmias. Currently, there are no studies that have examined how edema may influence changes in calcium dynamics in the functional syncytium. We performed optical mapping of calcium dynamics on a monolayer of neonatal rat cardiomyocytes with Fluo-4. The osmolality of the solutions was adjusted using the NaCl content. The initial Tyrode solution contained 140 mM NaCl (1T) and the hypoosmotic solutions contained 105 (0.75T) and 70 mM NaCl (0.5T). This study demonstrated a sharp decrease in the calcium wave propagation speed with a decrease in the solution osmolality. The successive decrease in osmolality also showed a transition from a normal wavefront to spiral wave and multiple wavelets of excitation with wave break. Our study demonstrated that, in a cellular model, hypoosmolality and, as a consequence, myocardial edema, could potentially lead to fatal ventricular arrhythmias, which to our knowledge has not been studied before. At 0.75T spiral waves appeared, whereas multiple wavelets of excitation occurred in 0.5T, which had not been recorded previously in a two-dimensional monolayer under conditions of cell edema without changes in the pacing protocol.

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.