THE ROLE OF INFLAMMATORY AND ANTI-INFLAMMATORY MEDIATORS IN ATHEROGENESIS
K.A. Lusta, A.N. Orekhov
The review presents the basic theories of the origin and development of atherosclerosis (AS), the main cause of cardiovascular disease. Emphasis is placed on the theory of inflammation, which is a central mechanism of atherogenesis. Among all the immune cells, monocyticmacrophages (MPh) are the major contributors to the atherosclerotic lesions of the vessel walls as they promote occurrence of the sites of arterial inflammation, produce reactive oxygen and nitrogen, secrete a variety of pro-inflammatory mediators in response to stimulation, phagocytize modified LDL and then are transformed into foam cells. The processes of MPhdifferentiation into proinflammatory (M1), anti-inflammatory (M2) and regulatory phenotypes are described and attention is paid to factors that induce MPh polarization. The transcription factors involved in the MPh differentiation and functioning are also outlined. The functions of the polarized MPh population are outlines with special attention to the description of produced cytokines, chemokines as well as M1 and M2 receptors. A separate section is also devoted to the results of immunohistochemical studies on the identification and localization of the main markers of M1 and M2 in the wall of the human aorta at different stages of AS lesions. The participation of T cells in atherogenesis as well as the importance of cell-cell interactions is described. The last section is devoted to the medical aspects of the study of AS processes. Elucidation the role of the balance between proinflammatory and anti-inflammatory factors in atherogenesis will allow developing new pharmacological and gene therapeutic treatments of this disease.
Key words: atherosclerosis, atherogenesis, aorta, immune cells, macrophages, monocytes, cytokines, chemokines, inflammatory mediators, transcription factors, immunohistochemistry