ArticleNature communications2024
PCSK9 stimulates Syk, PKCδ, and NF-κB, leading to atherosclerosis progression independently of LDL receptor.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
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Who cites it
43 citing papers in PubMed, 52 citations in OpenAlex.
- Loss of the Coronary Artery Disease Risk GeneCirculation · 2026Article
- PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes.Molecular medicine reports · 2026Article
- PCSK9 Predicts Adverse Limb Outcomes After Endovascular Revascularization in Diabetic Chronic Limb-threatening Ischemia.Thrombosis and haemostasis · 2026Article
- Targeting cytokine-like protein FAM3D alleviates atherosclerosis.Cell reports. Medicine · 2026Article
- PCSK9 in critical illness - It's not all about lipids.Annals of clinical biochemistry · 2026Review
- Review
- PROTAC-mediated PCSK9 degradation attenuates atherosclerosis and improves plaque composition via suppression of NF-κB/TNF-α pathway.BMC medicine · 2026Article
- PCSK9 in vascular smooth muscle cells: biology, pathology, and inhibition to fight atherosclerosis.Atherosclerosis plus · 2026Review
- Artificial intelligence-driven rational design and optimization of a potent terpenoid-derived PCSK9 inhibitor.Molecular diversity · 2026Article
- Statins, LDL-C and Beyond: A Contemporary Review of Atherosclerotic Cardiovascular Risk Assessment and Management.Journal of lipid and atherosclerosis · 2026Review
- Therapeutic Potential of PCSK9 Inhibitors in Regulating Neuroinflammation in Acute Ischemic Stroke.CNS drugs · 2026Review
- Alirocumab Attenuated Plaque Inflammation and PCSK9-Induced Proinflammatory Signalling in M1 Macrophages Independently of Lipid Lowering.Biomolecules · 2026Article
- Antisense Oligonucleotide Therapeutics Targeting Age-Related Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Article
- PCSK9 promotes atherosclerosis progression through the FOXO3a autophagy signaling pathway.Frontiers in cardiovascular medicine · 2026Article
- LDL receptor-independent mechanisms of proprotein convertase subtilisin/kexin type 9 in cardiovascular pathophysiology.Frontiers in cardiovascular medicine · 2026Review
- Integrating pharmacovigilance signals with real-world validation: a study on neurological events associated with PCSK9 inhibitors.Frontiers in medicine · 2026Article
- Proactive, short-term PCSK9 inhibition after PCI in patients with coronary artery disease at high residual risk: rationale and design of the randomized HANYANG-PICK trial.Frontiers in cardiovascular medicine · 2026Article
- Serum HMGB3 and PCSK9 Levels as Predictors of Early Treatment Response in PediatricInternational journal of general medicine · 2026Article
- PCSK9-Mediated Inflammation in Foam Cell Formation and Exploring the Biologically Active Compounds Derived From Natural Resources.Advances in pharmacological and pharmaceutical sciences · 2026Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Proprotein convertase subtilisin/kexin type-9 (PCSK9) binds to and degrades low-density lipoprotein (LDL) receptor, leading to increase of LDL cholesterol in blood. Its blockers have emerged as promising therapeutics for cardiovascular diseases. Here we show that PCSK9 itself directly induces inflammation and aggravates atherosclerosis independently of the LDL receptor. PCSK9 exacerbates atherosclerosis in LDL receptor knockout mice. Adenylyl cyclase-associated protein 1 (CAP1) is the main binding partner of PCSK9 and indispensable for the inflammatory action of PCSK9, including induction of cytokines, Toll like receptor 4, and scavenger receptors, enhancing the uptake of oxidized LDL. We find spleen tyrosine kinase (Syk) and protein kinase C delta (PKCδ) to be the key mediators of inflammation after PCSK9-CAP1 binding. In human peripheral blood mononuclear cells, serum PCSK9 levels are positively correlated with Syk, PKCδ, and p65 phosphorylation. The CAP1-fragment crystallizable region (CAP1-Fc) mitigates PCSK9-mediated inflammatory signal transduction more than the PCSK9 blocking antibody evolocumab does.
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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.