| Abstrakt: |
Atherogenesis begins with a disturbance in the homeostasis of atherogenic lipoproteins. An increase in their concentration in blood plasma leads to an increase in the endocytosis activity of endothelial cells. Lipoproteins penetrate through the transendothelial pathway into the intima tissue and through apo-B bind to glycosaminoglycans, connective tissue fibers. Remaining in it, they are exposed to the action of tissue enzymes, reactive oxygen species. Monocytes migrate to these “modified” particles by chemotaxis and transform into macrophages. They absorb “modified” lipoprotein particles occurs mainly through scavenger receptors. Macrophages turn into foam cells because their lysosomal enzymes are unable to cleave the polycyclic core of the cholesterol molecule. Macrophages/foam cells have relative deficiency of cholesterol esterase. Overflow of foam cells with cholesterol leads to damage to the membranes of phagolysosomes, the release of hydrolytic enzymes into the cytoplasm of the cell and its necrosis. At the same time, NLRP3 inflammasomes and the synthesis of interleukins 1β and 18 are activated. Damage to cytoplasmic membranes leads to the release of the contents of lysosomes and cholesterol into the intercellular space. As a result, inflammation occurs in the interstitial tissue of the intima. The lipids accumulated in the intima of the arteries, mainly cholesterol and its esters, become foreign bodies for this tissue. They induce chronic productive granulomatous inflammation. Smooth muscle cells and fibroblasts mobilized by macrophages produce connective tissue and isolate lipid deposits. In the nucleus of granulomas, there are cellular detritus, remnants of elastic and collagen fibers, foam cells, and cholesterol crystals. In large granulomas, neovascularization occurs due to tissue hypoxia. 10-20% of patients with coronary atherosclerosis develop "acute inflammation at the time of chronic inflammation". The cause of the exacerbation is damage to the fibrous capsules of granulomas and the endothelium covering them by lysosomal proteolytic enzymes. This starts the thrombotic process. Its consequence is myocardial infarction, thromboembolism, stroke, etc. It is possible to prevent the development of these complications by prescribing drugs that inhibit inflammation in granulomas. These include statins and TNF-α blockers. The point of view of some authors that modified LDL become antigens that cause autoimmune inflammation in the arteries is not convincing. Since structurally damaged macromolecules of lipoproteins in tissues are phagocytosed by macrophages, like other molecules, fragments of cells and tissues. [ABSTRACT FROM AUTHOR] |
