ArticleNature communications2017
Heparan sulfate proteoglycans present PCSK9 to the LDL receptor.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 115 citations in OpenAlex.
- Population-specific and trans-ancestry genome-wide analyses identify distinct and shared genetic risk loci for coronary artery disease.Nature genetics · 2020Pooled it
- Pooled it
- Review
- Study on the Role and Mechanism of γδ T Cells in Atherosclerosis Under a High-Fat Diet.Reviews in cardiovascular medicine · 2026Article
- Identification of flavonoids from natural products against hyperlipidaemia through computational approaches.PloS one · 2026Article
- AnCurrent pharmaceutical design · 2026Article
- Mechanisms of action and therapeutic potential of PCSK9-regulating drugs.Pharmaceutical biology · 2025Review
- Targeting Prostate Cancer Cells Using Anti-Sortilin and Anti-Syndecan-1 Antibody Drug Conjugates.International journal of molecular sciences · 2025Article
- Repurposed drugs as PCSK9-LDLR disruptors for lipid lowering and cardiovascular disease therapeutics.Molecular diversity · 2025Article
- LDL-Bound PCSK9 Has a Slower Clearance Kinetic and Higher Use for HSPGs Than Free-PCSK9-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Emerging roles of PCSK9 in kidney disease: lipid metabolism, megalin regulation and proteinuria.Pflugers Archiv : European journal of physiology · 2025Review
- Improving genetic variant identification for quantitative traits using ensemble learning-based approaches.BMC genomics · 2025Article
- Heparan sulfate chains in hepatocellular carcinoma.Gastroenterology report · 2025Review
- Immune-mediated renal injury in diabetic kidney disease: from mechanisms to therapy.Frontiers in immunology · 2025Review
- PCSK9 genetic variants and risk of vascular and non-vascular diseases in Chinese and UK populations.European journal of preventive cardiology · 2024Article
- PCSK9: From Nature's Loss to Patient's Gain.Circulation · 2024Article
- The role of proprotein convertase subtilisin/kexin 9 (PCSK9) in macrophage activation: a focus on its LDL receptor-independent mechanisms.Frontiers in cardiovascular medicine · 2024Review
- Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression.Scientific reports · 2023Article
- Computational Design, Synthesis, and Biological Evaluation of Diimidazole Analogues Endowed with Dual PCSK9/HMG-CoAR-Inhibiting Activity.Journal of medicinal chemistry · 2023Article
- 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
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Coronary artery disease is the main cause of death worldwide and accelerated by increased plasma levels of cholesterol-rich low-density lipoprotein particles (LDL). Circulating PCSK9 contributes to coronary artery disease by inducing lysosomal degradation of the LDL receptor (LDLR) in the liver and thereby reducing LDL clearance. Here, we show that liver heparan sulfate proteoglycans are PCSK9 receptors and essential for PCSK9-induced LDLR degradation. The heparan sulfate-binding site is located in the PCSK9 prodomain and formed by surface-exposed basic residues interacting with trisulfated heparan sulfate disaccharide repeats. Accordingly, heparan sulfate mimetics and monoclonal antibodies directed against the heparan sulfate-binding site are potent PCSK9 inhibitors. We propose that heparan sulfate proteoglycans lining the hepatocyte surface capture PCSK9 and facilitates subsequent PCSK9:LDLR complex formation. Our findings provide new insights into LDL biology and show that targeting PCSK9 using heparan sulfate mimetics is a potential therapeutic strategy in coronary artery disease.PCSK9 interacts with LDL receptor, causing its degradation, and consequently reduces the clearance of LDL. Here, Gustafsen et al. show that PCSK9 interacts with heparan sulfate proteoglycans and this binding favors LDLR degradation. Pharmacological inhibition of this binding can be exploited as therapeutic intervention to lower LDL levels.
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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.