Purpose Of Review: In the past 10 years, the LDL receptor inhibitor proprotein convertase subtilisin kexin type 9 (PCSK9) has emerged as a validated target for lowering plasma LDL cholesterol levels. Here we review the most recent reports on PCSK9 out of a total of 500 publications published in print or online before March 2013 and indexed on PubMed.
Recent Findings: All published in 2012, phase I and II clinical trials demonstrate that fully human monoclonal antibodies targeting PCSK9 dramatically reduce LDL-C and enable patients to reach their target goals, without severe or serious safety issues.
Summary: This review summarizes the discovery of PCSK9, its original mode of action as a secreted inhibitor of the LDL receptor, as well as its genetic regulation by statins. We then focus on the major results from the 2012 phase I and II PCSK9 inhibitor clinical trials. We also review the recent in-vivo studies demonstrating the potential cardiovascular benefits of long-term PCSK9 inhibition and discuss its potential side-effects.
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March 2025
Department of Pharmaceutical and Pharmacological Sciences, Padova, Italy.
Pharmacological inhibition of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) have been firmly established to be an effective approach to reduce low-density lipoprotein (LDL) cholesterol levels and cardiovascular events. Subcutaneous administration of monoclonal antibodies (evolocumab and alirocumab) every 2 or 4 weeks determined a 60 % reduction of LDL cholesterol levels, while the GalNac-siRNA anti PCSK9 (inclisiran) provided an effective lipid lowering activity (-50 %) after an initial subcutaneous dose, repeated after 3 months and followed by a maintenance dose every 6 months. Although these two approaches have the potentiality to bring the majority of patients at high and very-high cardiovascular risk to the appropriate LDL cholesterol targets, their cost and subcutaneous administration represent a strong limitation for their large-scale use.
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Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China.
Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality globally, with elevated low-density lipoprotein cholesterol (LDL-C) levels being a major risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in regulating LDL-C levels by promoting the degradation of hepatic low-density lipoprotein receptors (LDLR) responsible for clearing LDL-C from the circulation. PCSK9 inhibitors are novel lipid-modifying agents that have demonstrated remarkable efficacy in reducing plasma LDL-C levels and decreasing the incidence of CVD.
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Evaluating the effect of the antiPCSK9 vaccine on systemic inflammation and oxidative stress in CFA-challenged albino mice.
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Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Iran.
Background: To investigate whether the antiPCSK9 vaccine can affect the CRP and oxidative stress (OS) during acute systemic inflammation.
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