PCSK-9: modern views about biological role and possibilities of use as a diagnostic marker for cardiovascular diseases. Part 1

• Chaulin Aleksey M.
• Duplyakov Dmitriy V.

Abstract

In the first part of the literature review a brief historical digression on the PCSK-9 mechanism of action discovery and study is represented. The most important experimental works are described and analyzed. All of them were followed by a series of important discoveries, including creation of a new group of lipid-lowering agents - PCSK-9 inhibitors. Classification of mutations/polymorphisms that lead to an increase and a decrease in PCSK-9 activity is given. The main stages of PCSK-9 biosynthesis are discussed, in-depth study of which allowed to identify new potential targets for targeted blocking of PCSK-9. Recently discovered interesting PCSK-9 non-lipid effects are also reported. Among them: inflammatory reactions and processes of hemostasis that play an important role in etiology and pathogenesis of atherosclerosis and cardiovascular diseases.

In the second part of the review, PCSK-9 is considered as a biomarker of cardiovascular diseases. Methods for PCSK-9 concentration determination in healthy people and in category of patients with various cardiovascular abnormalities are represented. Prognostic significance of elevated PCSK-9 concentrations is discussed. According to numerous clinical trials PCSK-9 serum concentration can be connected with both metabolic parameters (fats, glucose, γ-glutamyltransferase, insulin, natriuretic peptides etc.) and clinical-functional data (gender, age, body mass index, vascular ultrasound parameters). Nevertheless, some studies have shown conflicting results: relatively wide variation of reference concentrations, as well as very weak or general lack of correlation with indicators that were described above. Sum it up so far we suspect potential reason and make an attempt to explain the conflicting results.

Keywords:literature review, PCSK-9, cholesterin, low-density lipoproteins, low-density lipoprotein receptors, atherosclerosis, inflammation, hemostasis

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