MECHANISMS OF ATHEROGENESIS AND ITS INTENSIFICATION IN PATIENTS WITH RHEUMATOID ARTHRITIS

Abstract

The article describes the role of cholesterol crystals (CS) in the mechanisms of development in the inner lining of arteries of inflammation – granulomatosis, induced by foreign bodies. The smallest CS crystals are found already in early atherosclerotic lesions. They are a factor in the initiation and exacerbation of atherosclerosis (At), cause cell damage and apoptosis. The formation of crystals within the necrotic nuclei of plaques can lead to an increase in their volume and to rupture. It has been shown that damage to the membranes of macrophages phagolysosomes by absorbed CS crystals leads to the inclusion of protein complexes – inflammasomes – in the inflammatory process, which trigger the inflammatory signaling cascade and are responsible for the secretion of pro-inflammatory cytokines. Inflammasomes NLRP3 are necessary for the process of atherogenesis; their activation is a link between the metabolism of cholesterol and inflammation involving macrophages. Unlike At, RA is manifested by autoimmune inflammation and immunocomplex vasculitis. When these diseases are combined, the effects of proinflammatory cytokines add up, an increase in the severity of inflammation, increased tissue damage and progression of atherosclerotic arterial lesions. The accelerated development of At in RA patients is facilitated by a combination of the action of traditional risk factors for atherogenesis and damage to the walls (endothelium) of arteries by immune complexes, complement, neutrophils and lymphocytes with an increase in their permeability to the lipid factor. The deposition of immune complexes in the capillaries of plaques leads to damage to their walls, destabilization of plaques and the development of acute cardiovascular events. The intensification of lipid accumulation and inflammation in the plaques of RA patients is confirmed in the section. Anticytokine drugs, primarily TNF-α and IL-1β antagonists, are pathogenetically substantiated agents for the progression of At in patients with RA. Statins remain a widely used class of drugs. They, in addition to hypolipidemic, immunomodulatory and anti-inflammatory effects, affect the crystallization of cholesterol, dissolve crystals and stabilize plaques.