Vol 1, No 2 (2022)

The Proprotein Convertase Subtilisin Kexin type 9 (PCSK9) protease is a 692 amino acid glycoprotein which belongs to the proprotein convertase family. PCSK9 binds several receptors of the LDL family, including VLDLR, LRP1 but also with CD36, driving their lysosomal degradation. From the beginning of the 21^st century a growing body of interest raised around the opportunity to pharmacologically inhibit PCSK9, and most recently, monoclonal antibodies have been successfully tested for the treatment of severe/genetic forms of dyslipidemia. Despite the majority of circulating PCSK9 being produced by the liver, other organs come into play contributing to its production, such as the heart, the pancreas, and the brain. Nonetheless, extrahepatic PCSK9 may exert a local/paracrine and or autocrine metabolic impact in the homeostatic regulation of cholesterol metabolism, suggesting that, opposite to the liver, in other tissue PCSK9 deficiency or inhibition could contribute to the development of specific organ and tissues dysfunctionalities.

Current clinical guidelines on lipid metabolism disorders are represented by the integration of relevant multicenter observational studies and registries aimed to identify best strategies in cardiovascular risk stratification, diagnostics and treatment of dyslipidemias. The approaches outlined in the European, Russian and American clinical guidelines look relevant to each other despite a range slightly different postulates, as they all demonstrate a general tendency to the importance of accurate risk stratification of patients and timely action on low-density lipoprotein cholesterol (LDL-C) levels when using effective lipid-lowering therapy.