PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD)

Overview

Journal Adv Pharm Bull

Date 2020 Oct 16

PMID 33062601

Citations 8

Authors

Saeideh Sobati

Amir Shakouri

Mahdi Edalati

Daryoush Mohammadnejad

Reza Parvan

Javad Masoumi

Jalal Abdolalizadeh

Affiliations

Soon will be listed here.

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9), as a vital modulator of low-density lipoprotein cholesterol (LDL-C) , is raised in hepatocytes and released into plasma where it binds to LDL receptors (LDLR), leading to their cleavage. PCSK9 adheres to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR which is confirmed by crystallography. LDLR expression is adjusted at the transcriptional level through sterol regulatory element binding protein 2 (SREBP-2) and at the post translational stages, specifically through PCSK9, and the inducible degrader of the LDLR PCSK9 inhibition is an appealing new method for reducing the concentration of LDL-C. In this review the role of PCSK9 in lipid homeostasis was elucidated, the effect of PCSK9 on atherosclerosis was highlighted, and contemporary therapeutic techniques that focused on PCSK9 were summarized. Several restoration methods to inhibit PCSK9 have been proposed which concentrate on both extracellular and intracellular PCSK9, and they include blockage of PCSK9 production by using gene silencing agents and blockage of it's binding to LDLR through antibodies and inhibition of PCSK9 autocatalytic processes by tiny molecule inhibitors.

Citing Articles

Effect of PCSK9 Inhibitors on Regulators of Lipoprotein Homeostasis, Inflammation and Coagulation.

Lunar P, Meglic H, Vehar M, Ugovsek S, Rehberger Likozar A, Sebestjen M Biomedicines. 2025; 13(2).

PMID: 40002707 PMC: 11852752. DOI: 10.3390/biomedicines13020294.

New epigenome players in the regulation of PCSK9-H3K4me3 and H3K9ac alterations by statin in hypercholesterolemia.

Duddu S, Katakia Y, Chakrabarti R, Sharma P, Shukla P J Lipid Res. 2024; 66(1):100699.

PMID: 39566851 PMC: 11699316. DOI: 10.1016/j.jlr.2024.100699.

Gene expression patterns of the LDL receptor and its inhibitor Pcsk9 in the adult zebrafish brain suggest a possible role in neurogenesis.

Gence L, Morello E, Rastegar S, Apalama M, Meilhac O, Bascands J Eur J Neurosci. 2024; 61(1):e16586.

PMID: 39551948 PMC: 11664473. DOI: 10.1111/ejn.16586.

The Application of Peptide Nucleic Acids (PNA) in the Inhibition of Proprotein Convertase Subtilisin/Kexin 9 () Gene Expression in a Cell-Free Transcription/Translation System.

Polak A, Machnik G, Buldak L, Ruczynski J, Prochera K, Bujak O Int J Mol Sci. 2024; 25(3).

PMID: 38338741 PMC: 10855603. DOI: 10.3390/ijms25031463.

Role of PCSK9 inhibition during the inflammatory stage of SARS-COV-2: an updated review.

Arsh H, Kumar F, Simran F, Tamang S, Rehman M, Ahmed G Ann Med Surg (Lond). 2024; 86(2):899-908.

PMID: 38333263 PMC: 10849418. DOI: 10.1097/MS9.0000000000001601.

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