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Updated: Aug 1, 2025
A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
Soluble PCSK9 Inhibition: Indications, Clinical Impact, New Molecular Insights and Practical Approach-Where Do We
Michele Bellino1, Gennaro Galasso1, Angelo Silverio1
1Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy.
Abstract:
Current research on cardiovascular prevention predominantly focuses on risk-stratification and management of patients with coronary artery disease (CAD) to optimize their prognosis. Several basic, translational and clinical research efforts aim to determine the etiological mechanisms underlying CAD pathogenesis and to identify lifestyle-dependent metabolic risk factors or genetic and epigenetic parameters responsible for CAD occurrence and/or progression. A log-linear association between the absolute exposure of LDL cholesterol (LDL-C) and the risk of atherosclerotic cardio-vascular disease (ASCVD) was well documented over the year. LDL-C was identified as the principal enemy to fight against, and soluble proprotein convertase subtilisin kexin type 9 (PCSK9) was attributed the role of a powerful regulator of blood LDL-C levels. The two currently available antibodies (alirocumab and evolocumab) against PCSK9 are fully human engineered IgG that bind to soluble PCSK9 and avoid its interaction with the LDLR. As documented by modern and dedicated "game-changer" trials, antibodies against soluble PCSK9 reduce LDL-C levels by at least 60 percent when used alone and up to 85 percent when used in combination with high-intensity statins and/or other hypolipidemic therapies, including ezetimibe. Their clinical indications are well established, but new areas of use are advocated. Several clues suggest that regulation of PCSK9 represents a cornerstone of cardiovascular prevention, partly because of some pleiotropic effects attributed to these newly developed drugs. New mechanisms of PCSK9 regulation are being explored, and further efforts need to be put in place to reach patients with these new therapies. The aim of this manuscript is to perform a narrative review of the literature on soluble PCSK9 inhibitor drugs, with a focus on their indications and clinical impact.
Insights
New PCSK9 inhibitor drugs significantly lower LDL cholesterol, offering a powerful new strategy for cardiovascular disease prevention. These therapies, including PCSK9 antibodies, are crucial for managing atherosclerotic cardiovascular disease risk.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Genetics
Background:
- Coronary artery disease (CAD) research focuses on risk stratification and management.
- Low-density lipoprotein cholesterol (LDL-C) is a primary risk factor for atherosclerotic cardiovascular disease (ASCVD).
- Soluble proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of LDL-C levels.
Purpose of the Study:
- To review the literature on soluble PCSK9 inhibitor drugs.
- To focus on the indications and clinical impact of PCSK9 inhibitors.
- To explore the role of PCSK9 regulation in cardiovascular prevention.
Main Methods:
- Narrative literature review.
- Analysis of clinical trial data on PCSK9 inhibitors.
- Examination of PCSK9's role in LDL-C regulation and cardiovascular risk.
Main Results:
- PCSK9 antibodies (alirocumab, evolocumab) reduce LDL-C by 60-85%.
- These antibodies are effective alone or with other lipid-lowering therapies.
- Established clinical indications exist, with potential for new applications.
Conclusions:
- PCSK9 inhibition is a cornerstone of cardiovascular prevention.
- PCSK9 inhibitors offer significant LDL-C reduction and potential pleiotropic effects.
- Further research and patient access to PCSK9 therapies are needed.
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