The consequences of PCSK9 inhibition in selected tissues

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of nine members of the proprotein convertase family. These serine proteases play a pivotal role in the post-translational modification of proteins and the activation of hormones, enzymes, transcription factors and growth factors. As a result, they participate in many physiological processes like embryogenesis, activity of central nervous system and lipid metabolism. Scientific studies show that the family of convertases is also involved in the pathogenesis of viral and bacterial infections, osteoporosis, hyperglycaemia, cardiovascular diseases, neurodegenerative disorders and cancer. The inhibition of PCSK9 by two currently approved for use monoclonal antibodies (alirocumab, evolocumab) slows down the degradation of low-density lipoprotein cholesterol receptors (LDLRs). This leads to increased density of LDLRs on the surface of hepatocytes, resulting in decreased level of low-density lipoprotein cholesterol (LDL-C) in the bloodstream, which is connected with the reduction of cardiovascular risk. PCSK9 inhibitors (PCSK9i) were created for the patients who could not achieve appropriate level of LDL-C using current statin and ezetimibe therapy. It seems that high therapeutic efficacy of PCSK9i will make them more common in the clinical use. The pleiotropic effects of previously mentioned lipid-lowering therapies were the reasons for literature review of possible positive and negative effects of PCSK9 inhibition beyond cholesterol metabolism.