ArticleJournal of lipid research2019
Cell-associated heparin-like molecules modulate the ability of LDL to regulate PCSK9 uptake.
Article in Journal of lipid research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 20 citations in OpenAlex.
- LDL-Bound PCSK9 Has a Slower Clearance Kinetic and Higher Use for HSPGs Than Free-PCSK9-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Characterization of Heparin Interactions With Recombinant Rodent Stabilin-2/Hyaluronic Acid Receptor for Endocytosis (HARE).Proteoglycan research · 2025Article
- Heparin Does Not Regulate Circulating Human PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) in a General Population-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- The Multifaceted Biology of PCSK9.Endocrine reviews · 2022Review
- Genetic and functional analyses detect an EXT1 splicing pathogenic variant in a Chinese hereditary multiple exostosis (HME) family.Molecular genetics & genomic medicine · 2022Article
- Pathogenic gain-of-function mutations in the prodomain and C-terminal domain of PCSK9 inhibit LDL binding.Frontiers in physiology · 2022Article
- Hepatic Sensing Loop Regulates PCSK9 Secretion in Response to Inhibitory Antibodies.Journal of the American College of Cardiology · 2021Article
- New Pharmacological Approaches to Target PCSK9.Current atherosclerosis reports · 2020Review
- A transient amphipathic helix in the prodomain of PCSK9 facilitates binding to low-density lipoprotein particles.The Journal of biological chemistry · 2020Article
- Proprotein convertase subtilisin/kexin type 9 and lipid metabolism.Current opinion in lipidology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) targets the LDL receptor (LDLR) for degradation, increasing plasma LDL and, consequently, cardiovascular risk. Uptake of secreted PCSK9 is required for its effect on the LDLR, and LDL itself inhibits this uptake, though how it does so remains unclear. In this study, we investigated the relationship between LDL, the PCSK9:LDLR interaction, and PCSK9 uptake. We show that LDL inhibits binding of PCSK9 to the LDLR in vitro more impressively than it inhibits PCSK9 uptake in cells. Furthermore, cell-surface heparin-like molecules (HLMs) can partly explain this difference, consistent with heparan sulfate proteoglycans (HSPGs) acting as coreceptors for PCSK9. We also show that HLMs can interact with either PCSK9 or LDL to modulate the inhibitory activity of LDL on PCSK9 uptake, with such inhibition rescued by competition with the entire PCSK9 prodomain, but not its truncated variants. Additionally, we show that the gain-of-function PCSK9 variant, S127R, located in the prodomain near the HSPG binding site, exhibits increased affinity for HLMs, potentially explaining its phenotype. Overall, our findings suggest a model where LDL acts as a negative regulator of PCSK9 function by decreasing its uptake via direct interactions with either the LDLR or HLMs.
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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.