Lipoproteins interact with immune cells, macrophages and endothelial cells - key players of the innate and adaptive immune system. High-density lipoprotein (HDL) particles seem to have evolved as part of the innate immune system since certain HDL subspecies contain combinations of apolipoproteins with immune regulatory functions. HDL is enriched in anti-inflammatory lipids, such as sphingosine-1-phosphate and certain saturated lysophospholipids. HDL reduces inflammation and protects against infection by modulating immune cell function, vasodilation and endothelial barrier function. HDL suppresses immune cell activation at least in part by modulating the cholesterol content in cholesterol/sphingolipid-rich membrane domains (lipid rafts), which play a critical role in the compartmentalization of signaling pathways. Acute infections, inflammation or autoimmune diseases lower HDL cholesterol levels and significantly alter HDL metabolism, composition and function. Such alterations could have a major impact on disease progression and may affect the risk for infections and cardiovascular disease. This review article aims to provide a comprehensive overview of the immune cell modulatory activities of HDL. We focus on newly discovered activities of HDL-associated apolipoproteins, enzymes, lipids, and HDL mimetic peptides.

https://www.mdpi.com/2227-9059/9/6/587/pdf

Current Understanding of the Immunomodulatory Activities of High-Density Lipoproteins.

Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored. 

/pdf/gut-microbiome-and-organ-fibrosis-37lz7xw8.pdf

Gut Microbiome and Organ Fibrosis

Atherosclerosis is one of the most important problems in modern medicine. Its high prevalence and social significance determine the need for a better understanding of the mechanisms of the disease’s development and progression. Lipid metabolism and its disorders are one of the key links in the pathogenesis of atherosclerosis. Lipids are involved in many processes, including those related to the mechanoreception of endothelial cells. The multifaceted role of lipids in endothelial mechanobiology and mechanisms of atherogenesis are discussed in this review. Endothelium is involved in ensuring adequate vascular hemodynamics, and changes in blood flow characteristics are detected by endothelial cells and affect their structure and function.

Diversity of Lipid Function in Atherogenesis: A Focus on Endothelial Mechanobiology.

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.

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

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.

/pdf/involvement-of-fatty-acids-and-their-metabolites-in-the-30ptua1z.pdf

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

Chronic obstructive pulmonary disease (COPD) is a widespread socially significant disease. The development of COPD involves the innate immune system. Interestingly, the regulation of the innate lung immune system is related to the gut microbiota. This connection is due to the production by gut microorganisms of short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate. Nutritional disturbances and changes in the structure of the intestinal microbiota lead to a decrease in SCFAs production and their effect on pulmonary immunity. The presence of a metabolic and immune axis linking the lungs and gut plays an important role in the pathogenesis of COPD. In addition, the nature of nutrition and SCFAs may participate in the development of the clinically heterogeneous course of COPD.

/pdf/role-of-short-chain-fatty-acids-produced-by-gut-microbiota-12hsnv15.pdf

Role of Short-Chain Fatty Acids Produced by Gut Microbiota in Innate Lung Immunity and Pathogenesis of the Heterogeneous Course of Chronic Obstructive Pulmonary Disease

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.

Stanislav Kotlyarov

Papers

Diversity of Lipid Function in Atherogenesis: A Focus on Endothelial Mechanobiology.

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

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

Role of Short-Chain Fatty Acids Produced by Gut Microbiota in Innate Lung Immunity and Pathogenesis of the Heterogeneous Course of Chronic Obstructive Pulmonary Disease

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