ON THE ROLE OF PCSK9 IN THE DEVELOPMENT OF ATHEROSCLEROSIS: MOLECULAR ASPECTS

DOI: https://doi.org/10.29296/24999490-2021-02-02

A.M. Chaulin(1, 2), D.V. Duplyakov(1, 2) 1-Samara Regional Cardiological Dispensary, Aerodromnaya str, 43, Samara, 443070, Russian Federation; 2-Samara State Medical University, Chapaevskaya St., 89, Samara, 443099, Russian Federation E-mail: [email protected]

Due to the discovery of the proprotein convertase subtilisin/kexin type 9 (PCSK9) and the establishment of its role in lipoprotein metabolism, it became possible to deliver new groups of effective drugs for the treatment of dyslipidemia. The main function of PCSK9 is to eliminate low-density lipoprotein receptors leading to the development of hypercholesterolemia – one of the key risk factors for atherosclerosis and cardiovascular diseases. Therefore, inhibition of PCSK9 has become a new strategy for hypolipidemic measures. Monoclonal antibodies (class G immunoglobulins) against PCSK9 – alirocumab and evolocumab are currently approved for the use in clinical practice. At the stage of development and clinical trials, there are many additional groups of drugs acting as inhibition of PCSK9 gene expression, PCSK9 matrix RNA translation, and inhibition of the function of the PCSK9 enzyme. This review examines the role of PCSK9 in the regulation of lipoprotein metabolism and describes in detail the molecular mechanisms for regulating the expression of the gene encoding PCSK9. The main groups of new hypolipidemic anti-PCSK9 drugs are also discussed: monoclonal antibodies against PCSK9, small interfering RNAs, antisense nucleotides, small molecules, and the anti-PCSK9 vaccine
Keywords: 
cardiovascular diseases, atherosclerosis, PCSK9, low-density lipoproteins, monoclonal antibodies, small interfering RNAS, antisense nucleotides, annexin A2, CRISPR/Cas9, vaccine
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