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

Sobati, Saeideh, Shakouri, Amir, Edalati, Mahdi, Mohammadnejad, Daryoush, Parvan, Reza, Masoumi, Javad, Abdolalizadeh, Jalal·2020·Advanced Pharmaceutical Bulletin
DOI 10.34172/apb.2020.062PMC PMC7539318
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Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9), as a vital modulator of low-densitylipoprotein cholesterol (LDL-C) , is raised in hepatocytes and released into plasma where it bindsto LDL receptors (LDLR), leading to their cleavage. PCSK9 adheres to the epidermal growthfactor-like repeat A (EGF-A) domain of the LDLR which is confirmed by crystallography. LDLRexpression is adjusted at the transcriptional level through sterol regulatory element bindingprotein 2 (SREBP-2) and at the post translational stages, specifically through PCSK9, and theinducible degrader of the LDLR PCSK9 inhibition is an appealing new method for reducing theconcentration of LDL-C. In this review the role of PCSK9 in lipid homeostasis was elucidated, theeffect of PCSK9 on atherosclerosis was highlighted, and contemporary therapeutic techniquesthat focused on PCSK9 were summarized. Several restoration methods to inhibit PCSK9 havebeen proposed which concentrate on both extracellular and intracellular PCSK9, and theyinclude blockage of PCSK9 production by using gene silencing agents and blockage of it’sbinding to LDLR through antibodies and inhibition of PCSK9 autocatalytic processes by tinymolecule inhibitors.

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Metadata

Authors
Sobati, S., Shakouri, A., Edalati, M., Mohammadnejad, D., Parvan, R., Masoumi, J., & Abdolalizadeh, J.
Affiliations
  • Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
  • Department of Biosciences, University of Milan, Via celoria 26, 20133, Milan, Italy.
  • Immunology Department, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
  • Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
ORCID
Abdolalizadeh, Jalal
Venue
Advanced Pharmaceutical Bulletin
Publisher
Maad Rayan Publishing Company
Published
2020-08-09
Volume
10
Issue
4
Pages
502-511
ISSN
  • 2228-5881
  • 2251-7308
DOI
10.34172/apb.2020.062
PMC
PMC7539318
Cited by
33
References
6
Language
en

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