Amir Abbas Momtazi-Borojeni, Matteo Pirro, Suowen Xu and Amirhossein Sahebkar* Pages 980 - 999 ( 20 )
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9-I) are novel therapeutic tools to decrease cardiovascular risk. These agents work by lowering the low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients who are statin resistant/intolerant. Current clinically approved and investigational PCSK9- I act generally by blocking PCSK9 activity in the plasma or suppressing its expression or secretion by hepatocytes. The most widely investigated method is the disruption of PCSK9/LDL receptor (LDLR) interaction by fully-humanized monoclonal antibodies (mAbs), evolocumab and alirocumab, which have been approved for the therapy of hypercholesterolemia and atherosclerotic cardiovascular disease (CVD). Besides, a small interfering RNA called inclisiran, which specifically suppresses PCSK9 expression in hepatocytes, is as effective as mAbs but with administration twice a year. Because of the high costs of such therapeutic approaches, several other PCSK9-I have been surveyed, including peptide-based anti-PCSK9 vaccines and small oral anti-PCSK9 molecules, which are under investigation in preclinical and phase I clinical studies. Interestingly, anti-PCSK9 vaccination has been found to serve as a more widely feasible and more cost-effective therapeutic tool over mAb PCSK9-I for managing hypercholesterolemia. The present review will discuss LDL-lowering and cardioprotective effects of PCSK9-I, mainly immunotherapy- based inhibitors including mAbs and vaccines, in preclinical and clinical studies.
Alirocumab , evolocumab , immunotherapy , inclisiran , PCSK9 , vaccine .
Iran's National Elites Foundation, Unit of Internal Medicine, Department of Medicine, University of Perugia, Perugia, 06129, Department of Endocrinology, First Affiliated Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad