TO THE PATHOGENESIS AND MORPHOGENESIS OF ATHEROSCLEROSIS

The history of the study of atherosclerosis is full of both discoveries and disappointments, both dogmas that hindered the process of understanding the causes of the disease, and revolutionary breakthroughs in clarifying the mechanisms of its formation. But there are even more hypotheses and questions left by previous generations of researchers, which were not easy to confirm. The use of cell cultures, the study of lipid metabolism at the molecular level, mutations and gene expression, enzyme immunoassay, assessment of the state of cell receptors, the study of the cytokine system and many other modern research methods have revealed the essence of a number of mechanisms of atherosclerosis, showed the complex nature of this process [1]. Atherosclerosis is the main cause of death in developed countries. This is a progressive pathological process that begins in childhood and gives  clinical manifestations in the middle of adulthood [2]. The presented data indicate the role of inflammation as a determinant of the biology underlying the complications of atherosclerosis and it should be emphasized that the deepening of knowledge in the field of the pathogenesis of atherosclerosis  opens up new ways to prevent and treat this severe and widespread disease [3, 4, 5]. One of the ways to modify LDL located in the subendothelial space is oxidation. It is carried out due to the local effect of reactive oxygen radicals and pro-oxidant enzymes formed in the activated endothelium and in smooth muscle cells, as well as in macrophages that have penetrated the vessel wall. In addition, the microenvironment in the subendothelial space is able to bind oxidized LDL from plasma antioxidants. The mobilization of leukocytes (mainly monocytes and T-lymphocytes) is expressed in their predominant localization on the vascular wall and serves as a key pathogenetic process of atherogenesis. Modified LDL and cytokines (IL-1, TNF-a) independently induce the expression of leukocyte adhesion molecules (MAL) and the chemoattractant cytokine (chemokine). However, MLPNPS are also powerful stimulators of the production of inflammatory mediators, cytokines by endothelial and smooth muscle cells, thereby enhancing the direct effect [6]. This dual ability of mLPNP to cause leukocyte mobilization and inflammation is maintained in one way or another throughout the atherogenic process. While endothelial cells play a certain role in the formation of fat strips, the migration of smooth muscle cells into intima serves as the dominant process in the early stages of the formation of fibrous plaques [7, 8, 9, 10, 11, 12].

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