ReviewCardiovascular research2019
Novel strategies to target proprotein convertase subtilisin kexin 9: beyond monoclonal antibodies.
Review in Cardiovascular research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 93 citations in OpenAlex.
- High levels of serum cholesterol increase the risk of developing vessel co-opting tumors in colorectal cancer liver metastases.The FEBS journal · 2026Article
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach.European journal of medical research · 2025Review
- The importance of paying attention to the role of lipid-lowering drugs in controlling dengue virus infection.Virology journal · 2024Review
- ASGR1 deficiency improves atherosclerosis but alters liver metabolism in ApoECardiovascular diabetology · 2024Article
- Article
- Potential use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and prevention method in viral infection.Microbial cell factories · 2024Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
- Article
- Genetic evidence implicating circulating lipids and lipid drug targets in pterygium.Computational and structural biotechnology journal · 2023Article
- PCSK9 Inhibitor Wars: How Does Inclisiran Fit in with Current Monoclonal Antibody Inhibitor Therapy? Considerations for Patient Selection.Current cardiology reports · 2022Review
- Expanding Biology of PCSK9: Roles in Atherosclerosis and Beyond.Current atherosclerosis reports · 2022Review
- Inclisiran: How Widely and When Should We Use It?Current atherosclerosis reports · 2022Review
- [Update on PCSK9 inhibition].Herz · 2022Review
- The Multifaceted Biology of PCSK9.Endocrine reviews · 2022Review
- Inflammation and atherosclerosis: signaling pathways and therapeutic intervention.Signal transduction and targeted therapy · 2022Review
- Effects of PCSK9 Targeting: Alleviating Oxidation, Inflammation, and Atherosclerosis.Journal of the American Heart Association · 2022Review
- Gene Therapy TargetingMetabolites · 2022Review
- Crosstalk between dendritic cells and T lymphocytes during atherogenesis: Focus on antigen presentation and break of tolerance.Frontiers in cardiovascular medicine · 2022Review
- LDL-Cholesterol-Lowering Therapy.Handbook of experimental pharmacology · 2022Article
- The Association of Proprotein Convertase Subtilisin/Kexin Type 9 to Plasma Low-Density Lipoproteins: An Evaluation of Different Methods.Metabolites · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Since the discovery of the role of proprotein convertase subtilisin kexin 9 (PCSK9) in the regulation of low-density lipoprotein cholesterol (LDL-C) in 2003, a paradigm shift in the treatment of hypercholesterolaemia has occurred. The PCSK9 secreted into the circulation is a major downregulator of the low-density lipoprotein receptor (LDLR) protein, as it chaperones it to endosomes/lysosomes for degradation. Humans with loss-of-function of PCSK9 exhibit exceedingly low levels of LDL-C and are protected from atherosclerosis. As a consequence, innovative strategies to modulate the levels of PCSK9 have been developed. Since 2015 inhibitory monoclonal antibodies (evolocumab and alirocumab) are commercially available. When subcutaneously injected every 2-4 weeks, they trigger a ∼60% LDL-C lowering and a 15% reduction in the risk of cardiovascular events. Another promising approach consists of a liver-targetable specific PCSK9 siRNA which results in ∼50-60% LDL-C lowering that lasts up to 6 months (Phases II-III clinical trials). Other strategies under consideration include: (i) antibodies targeting the C-terminal domain of PCSK9, thereby inhibiting the trafficking of PCSK9-LDLR to lysosomes; (ii) small molecules that either prevent PCSK9 binding to the LDLR, its trafficking to lysosomes or its secretion from cells; (iii) complete silencing of PCSK9 by CRISPR-Cas9 strategies; (iv) PCSK9 vaccines that inhibit the activity of circulating PCSK9. Time will tell whether other strategies can be as potent and safe as monoclonal antibodies to lower LDL-C levels.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.