MODERN OPPORTUNITIES OF ATHEROSCLEROSIS PHARMACOTHERAPY: NEW DIRECTIONS

Abstract

Despite the successful achievements in modern applied medicine and the application of hypolipidemic drugs into clinical practice for the past 50 years, the issue of prevention and treatment of atherosclerotic vascular disease (AVD) remains unsolved. Implementation of the theory of immunopathogenesis of atherosclerosis that was experimentally proved by modern studies allows the specialists to expand the possibilities of pharmacotherapy and pharmacoprevention for AVD. Thus, the aim of the present study was to analyze new directions in the development of anti-atherosclerotic drugs (AAD) with a pathogenetic activity that suppressed chronic autoimmune inflammation in the areas of atherosclerotic damage of vessels. In the course of the study, the search and analysis of the publications in the databases Web of Science, PubMed, and RSCI (Russian Science Citation Index) for the period of 2016-2018 were performed. According to the performed analysis, the most perspective molecular targets for AAD are pro-inflammatory and anti-inflammatory cytokines that develop a disbalance in patients with AVD. Thus, the drugs that are based on monoclonal antibodies to the tumor necrosis factor α (TNFα), and pro-inflammatory interleukins (1β, 17А), used for the treatment of rheumatoid arthritis and psoriasis, can be used for the treatment of AVD. Recombinant interleukins 6, 13, 19, and substances that suppress the expression of interferon regulatory factors will also exert an antiatherogenic effect. The studies on the modeling of the pathogenesis of AVD in inbred animals showed that other molecular targets for AAD could be enzymes involved in the lipid and immune cells metabolism. They include inositol requiring enzyme 1, proprotein convertase subtilisin/Kexin type 9, and the enzymes of paraoxonase family. Besides, the review includes the discussion of the successful application of drugs based on monoclonal antibodies to TNFα (infliximab), IL-17A (secukinumab) and IL-1β (canakinumab), as well as the drugs with antienzymatic activity (evolocumab and darapladib), in clinical practice for the treatment of AVD. The modern knowledge on molecular mechanisms of immunopathogenesis can give grounds for the development of drugs for pathogenetic pharmacotherapy and pharmacoprevention for the complications of AVD. The most effective solution would be the indication of drugs that affect the disbalance of cytokines and metabolic processes in the immune cells.