Participation of Krüppel-like Factors in Atherogenesis.

Atherosclerosis is an important problem in modern medicine, the keys to understanding many aspects of which are still not available to clinicians. Atherosclerosis develops as a result of a complex chain of events in which many cells of the vascular wall and peripheral blood flow are involved. Endothelial cells, which line the vascular wall in a monolayer, play an important role in vascular biology. A growing body of evidence strengthens the understanding of the multifaceted functions of endothelial cells, which not only organize the barrier between blood flow and tissues but also act as regulators of hemodynamics and play an important role in regulating the function of other cells in the vascular wall. Krüppel-like factors (KLFs) perform several biological functions in various cells of the vascular wall. The large family of KLFs in humans includes 18 members, among which KLF2 and KLF4 are at the crossroads between endothelial cell mechanobiology and immunometabolism, which play important roles in both the normal vascular wall and atherosclerosis.

The Importance of the Plasma Membrane in Atherogenesis.

Atherosclerotic cardiovascular diseases are an important medical problem due to their high prevalence, impact on quality of life and prognosis. The pathogenesis of atherosclerosis is an urgent medical and social problem, the solution of which may improve the quality of diagnosis and treatment of patients. Atherosclerosis is a complex chain of events, which proceeds over many years and in which many cells in the bloodstream and the vascular wall are involved. A growing body of evidence suggests that there are complex, closely linked molecular mechanisms that occur in the plasma membranes of cells involved in atherogenesis. Lipid transport, innate immune system receptor function, and hemodynamic regulation are linked to plasma membranes and their biophysical properties. A better understanding of these interrelationships will improve diagnostic quality and treatment efficacy.

Clinical Significance of Lipid Transport Function of ABC Transporters in the Innate Immune System.

ABC transporters are a large family of proteins that transport a variety of substrates across cell plasma membranes. Because of this, they are involved in many physiological processes. It is of interest to note that many ABC transporters are involved in the transport of various lipids. In addition, this function may be related to the innate immune system. The evidence that ABC transporters are involved in the regulation of the innate immune system through the transport of various substances greatly enhances the understanding of their clinical significance. ABC transporters are involved in the cellular homeostasis of cholesterol as well as in the regulation of its content in lipid rafts. Through these mechanisms, they can regulate the function of membrane proteins, including receptors of the innate immune system. By regulating lipid transport, some members of ABC transporters are involved in phagocytosis. In addition, ABC transporters are involved in the transport of lipopolysaccharide, lipid mediators of inflammation, and perform other functions in the innate immune system.

Clinical significance of polyunsaturated fatty acids in the prevention of cardiovascular diseases.

Cardiovascular diseases are one of the most important problems of modern medicine. They are associated with a large number of health care visits, hospitalizations and mortality. Prevention of atherosclerosis is one of the most effective strategies and should start as early as possible. Correction of lipid metabolism disorders is associated with definite clinical successes, both in primary prevention and in the prevention of complications of many cardiovascular diseases. A growing body of evidence suggests a multifaceted role for polyunsaturated fatty acids. They demonstrate a variety of functions in inflammation, both participating directly in a number of cellular processes and acting as a precursor for subsequent biosynthesis of lipid mediators. Extensive clinical data also support the importance of polyunsaturated fatty acids, but all questions have not been answered to date, indicating the need for further research.

Molecular Pharmacology of Inflammation Resolution in Atherosclerosis.

Atherosclerosis is one of the most important problems of modern medicine as it is the leading cause of hospitalizations, disability, and mortality. The key role in the development and progression of atherosclerosis is the imbalance between the activation of inflammation in the vascular wall and the mechanisms of its control. The resolution of inflammation is the most important physiological mechanism that is impaired in atherosclerosis. The resolution of inflammation has complex, not fully known mechanisms, in which lipid mediators derived from polyunsaturated fatty acids (PUFAs) play an important role. Specialized pro-resolving mediators (SPMs) represent a group of substances that carry out inflammation resolution and may play an important role in the pathogenesis of atherosclerosis. SPMs include lipoxins, resolvins, maresins, and protectins, which are formed from PUFAs and regulate many processes related to the active resolution of inflammation. Given the physiological importance of these substances, studies examining the possibility of pharmacological effects on inflammation resolution are of interest.

Involvement of Fatty Acids and Their Metabolites in the Development of Inflammation in Atherosclerosis.

Despite all the advances of modern medicine, atherosclerosis continues to be one of the most important medical and social problems. Atherosclerosis is the cause of several cardiovascular diseases, which are associated with high rates of disability and mortality. The development of atherosclerosis is associated with the accumulation of lipids in the arterial intima and the disruption of mechanisms that maintain the balance between the development and resolution of inflammation. Fatty acids are involved in many mechanisms of inflammation development and maintenance. Endothelial cells demonstrate multiple cross-linkages between lipid metabolism and innate immunity. In addition, these processes are linked to hemodynamics and the function of other cells in the vascular wall, highlighting the central role of the endothelium in vascular biology.

Anti-Inflammatory Function of Fatty Acids and Involvement of Their Metabolites in the Resolution of Inflammation in Chronic Obstructive Pulmonary Disease.

Lipid metabolism plays an important role in many lung functions. Disorders of lipid metabolism are part of the pathogenesis of chronic obstructive pulmonary disease (COPD). Lipids are involved in numerous cross-linkages with inflammation. Recent studies strongly support the involvement of fatty acids as participants in inflammation. They are involved in the initiation and resolution of inflammation, including acting as a substrate for the formation of lipid mediators of inflammation resolution. Specialized pro-inflammatory mediators (SPMs) belonging to the classes of lipoxins, resolvins, maresins, and protectins, which are formed enzymatically from unsaturated fatty acids, are now described. Disorders of their production and function are part of the pathogenesis of COPD. SPMs are currently the subject of active research in order to find new drugs. Short-chain fatty acids are another important participant in metabolic and immune processes, and their role in the pathogenesis of COPD is of great clinical interest.

Bioinformatic Analysis of ABCA1 Gene Expression in Smoking and Chronic Obstructive Pulmonary Disease.

Smoking is a key modifiable risk factor for developing the chronic obstructive pulmonary disease (COPD). When smoking, many processes, including the reverse transport of cholesterol mediated by the ATP binding cassette transporter A1 (ABCA1) protein are disrupted in the lungs. Changes in the cholesterol content in the lipid rafts of plasma membranes can modulate the function of transmembrane proteins localized in them. It is believed that this mechanism participates in increasing the inflammation in COPD. METHODS: Bioinformatic analysis of datasets from Gene Expression Omnibus (GEO) was carried out. Gene expression data from datasets of alveolar macrophages and the epithelium of the respiratory tract in smokers and COPD patients compared with non-smokers were used for the analysis. To evaluate differentially expressed genes, bioinformatic analysis was performed in comparison groups using the limma package in R (v. 4.0.2), and the GEO2R and Phantasus tools (v. 1.11.0). RESULTS: The conducted bioinformatic analysis showed changes in the expression of the ABCA1 gene associated with smoking. In the alveolar macrophages of smokers, the expression levels of ABCA1 were lower than in non-smokers. At the same time, in most of the airway epithelial datasets, gene expression did not show any difference between the groups of smokers and non-smokers. In addition, it was shown that the expression of ABCA1 in the epithelial cells of the trachea and large bronchi is higher than in small bronchi. CONCLUSIONS: The conducted bioinformatic analysis showed that smoking can influence the expression of the ABCA1 gene, thereby modulating lipid transport processes in macrophages, which are part of the mechanisms of inflammation development.

The Role of ABC Transporters in Lipid Metabolism and the Comorbid Course of Chronic Obstructive Pulmonary Disease and Atherosclerosis.

Chronic obstructive pulmonary disease (COPD) ranks among the leading causes of morbidity and mortality worldwide. COPD rarely occurs in isolation and is often combined with various diseases. It is considered that systemic inflammation underlies the comorbid course of COPD. The data obtained in recent years have shown the importance of violations of the cross-links of lipid metabolism and the immune response, which are links in the pathogenesis of both COPD and atherosclerosis. The role of lipid metabolism disorders in the pathogenesis of the comorbid course of COPD and atherosclerosis and the participation of ATP-binding cassette (ABC) transporters in these processes is discussed in this article. It is known that about 20 representatives of a large family of ABC transporters provide lipid homeostasis of cells by moving lipids inside the cell and in its plasma membrane, as well as removing lipids from the cell. It was shown that some representatives of the ABC-transporter family are involved in various links of the pathogenesis of COPD and atherosclerosis, which can determine their comorbid course.

Molecular Mechanisms of Lipid Metabolism Disorders in Infectious Exacerbations of Chronic Obstructive Pulmonary Disease.

Exacerbations largely determine the character of the progression and prognosis of chronic obstructive pulmonary disease (COPD). Exacerbations are connected with changes in the microbiological landscape in the bronchi due to a violation of their immune homeostasis. Many metabolic and immune processes involved in COPD progression are associated with bacterial colonization of the bronchi. The objective of this review is the analysis of the molecular mechanisms of lipid metabolism and immune response disorders in the lungs in COPD exacerbations. The complex role of lipid metabolism disorders in the pathogenesis of some infections is only beginning to be understood, however, there are already fewer and fewer doubts even now about its significance both in the pathogenesis of infectious exacerbations of COPD and in general in the progression of the disease. It is shown that the lipid rafts of the plasma membranes of cells are involved in many processes related to the detection of pathogens, signal transduction, the penetration of pathogens into the cell. Smoking disrupts the normally proceeded processes of lipid metabolism in the lungs, which is a part of the COPD pathogenesis.