Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Nov 22:6:212511.
doi: 10.7573/dic.212511. eCollection 2017.

Lipid-lowering interventions targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): an emerging chapter in lipid-lowering therapy

Constantine E Kosmas  1 , Eddy DeJesus  2 , Rosmery Morcelo  3 , Frank Garcia  3 , Peter D Montan  3 , Eliscer Guzman  4
Affiliations
Review

Lipid-lowering interventions targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): an emerging chapter in lipid-lowering therapy

Constantine E Kosmas et al. Drugs Context. .

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is mainly expressed in the liver but can also be found in the intestine and kidneys. PCSK9 promotes the degradation of low density lipoprotein receptors (LDLR) by reducing their recycling and targeting the receptors for lysosomal destruction, thereby decreasing the rate of removal of LDL-cholesterol from the circulation. Thus, interventions targeting PCSK9 by reducing its expression may lead to significant reductions of LDL-cholesterol and possibly decrease cardiovascular risk. The present review aims to present and discuss the current clinical and scientific data pertaining to lipid-lowering interventions targeting PCSK9.

Keywords: AT04A vaccine; LDL-C; LDLR; PCSK9; low density lipoprotein cholesterol; low density lipoprotein receptors; proprotein convertase subtilisin/kexin type 9; siRNA; small interfering RNA.

PubMed Disclaimer

Conflict of interest statement

Disclosure and potential conflicts of interest: Constantine E Kosmas is a member of the Dyslipidemia Speaker Bureau of Amgen, Inc. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors are available for download at http://www.drugsincontext.com/wp-content/uploads/2017/11/dic.212511-COI.pdf

References

    1. Jones PH, Nair R, Thakker KM. Prevalence of dyslipidemia and lipid goal attainment in statin-treated subjects from 3 data sources: a retrospective analysis. J Am Heart Assoc. 2012;1(6):e001800. doi: 10.1161/JAHA.112.001800. - DOI - PMC - PubMed
    1. Kosmas CE, Frishman WH. New and emerging LDL cholesterol-lowering drugs. Am J Ther. 2015;22(3):234–41. doi: 10.1097/MJT.0000000000000063. - DOI - PubMed
    1. Seidah NG, Prat A. The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Discov. 2012;11(5):367–83. doi: 10.1038/nrd3699. - DOI - PubMed
    1. Leren TP. Sorting an LDL receptor with bound PCSK9 to intracellular degradation. Atherosclerosis. 2014;237(1):76–81. doi: 10.1016/j.atherosclerosis.2014.08.038. - DOI - PubMed
    1. Lambert G, Charlton F, Rye KA, Piper DE. Molecular basis of PCSK9 function. Atherosclerosis. 2009;203(1):1–7. doi: 10.1016/j.atherosclerosis.2008.06.010. - DOI - PubMed