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.

Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. From a modern point of view, endothelial dysfunction is considered as a key factor leading to the development of CVD. However, scientists have suggested that the main causes of the development of CVD might be functional disorders and phenotypic modulation of smooth muscle cells (SMCs) that make up the vascular wall. In this regard, the aim of our study was to evaluate the functional features of SMCs isolated from the tunica intima and from the tunica media of the thoracic part of the human aorta in patients with CVD. In our research we showed that phenotypic switching can occur in SMCs isolated from patients with aneurysms (n = 6), resulting in remodeling of the extracellular matrix and impaired interaction between cellular receptors. In addition, it is probable that the activation of complement-mediated phagocytosis as a result of LDL internalization by SMCs might be one of the key mechanisms in the process of aneurysm development.

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.

The aorta is the largest blood vessel in the body, which reaches a diameter of about 3 cm and is responsible for transporting oxygen-enriched arterial blood from the heart to tissues and organs. The aortic wall consists of three layers: the inner Tunica intima, the middle Tunica media and the outer Tunica adventitia. The layers of the aortic wall have a diverse cellular composition and include smooth muscle cells (SMCs), fibroblasts, endothelial cells, etc. Functional disorders in the cells of the intima of the human aorta can lead to various cardiovascular diseases (СVD), such as aneurysm and, as a result, dissection or rupture of the thoracic aorta. The cellular and molecular mechanisms of CVD development remain not fully understood, therefore, the study of the functional characteristics of various cell populations that make up the human aorta is an urgent task today. The aim is to evaluate the inflammatory response formed by cells that are part of the Tunica intima of the human aorta during phagocytosis of latex particles and internalization of low-density lipoproteins (LDL) to study their role in the development of aneurysms. The experiments were performed on smooth muscle cells (SMCs) isolated from the intima of the human aorta in patients with aneurysm. Phagocytic activity was studied by adding latex beads to the SMCs of Tunica intima, the ability to internalize LDL was evaluated using the BDP 630/650 dye and a biochemical method, the assessment of the ability to pro- and anti-inflammatory activation was studied using enzyme-linked immunosorbent assay (ELISA). Our results demonstrated that the absorption of latex beads and LDL stimulates the activation of interleukin secretion by smooth muscle cells that are part of the Tunica intima of the aorta, namely the proinflammatory cytokines IL-6 and IL-8. This fact may indicate that in the conditions of the body, the human aortic intima SMCs phenotype may switch from contractile to secretory or macrophage-like, which indicates the participation of this phenotypic cell transition in the process of aneurysm development.