ArticleInternational journal of molecular sciences2021
PCSK9 Induces Tissue Factor Expression by Activation of TLR4/NFkB Signaling.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- PCSK9 inhibitors in neurodegenerative disorders: mechanisms, therapeutic potential, and clinical implications.Translational neurodegeneration · 2026Review
- PCSK9 at the intersection of lipid metabolism, immunometabolism, and psychiatric disorders: A narrative review.Brain, behavior, & immunity - health · 2026Review
- Evolocumab-associated haemorrhagic pericarditis with cardiac tamponade: case report.European heart journal. Case reports · 2026Article
- PCSK9 in vascular smooth muscle cells: biology, pathology, and inhibition to fight atherosclerosis.Atherosclerosis plus · 2026Review
- Aspirin Eugenol Ester Ameliorates Fatty Liver Hemorrhagic Syndrome in Laying Hens by Reducing Oxidative Stress and Inflammation.International journal of molecular sciences · 2026Article
- Molecular and Genetic Aspects of Lipid Metabolism Disorders and Potential Targets for Gene Therapy.Journal of lipid and atherosclerosis · 2026Review
- Alirocumab Attenuated Plaque Inflammation and PCSK9-Induced Proinflammatory Signalling in M1 Macrophages Independently of Lipid Lowering.Biomolecules · 2026Article
- Article
- LDL receptor-independent mechanisms of proprotein convertase subtilisin/kexin type 9 in cardiovascular pathophysiology.Frontiers in cardiovascular medicine · 2026Review
- Upregulated PCSK9 Level Contributes to Human Pulmonary Microvascular Endothelial Cell Apoptosis in Cigarette Smoke Extract-Induced COPD Models Through TLR4/NF-kappaB Pathway Activation.Applied biochemistry and biotechnology · 2025Article
- The Impact of PCSK9 on Diabetic Cardiomyopathy: Mechanisms and Implications.Biomolecules · 2025Review
- Intersecting Pathways of Inflammation, Oxidative Stress, and Atherogenesis in the Evaluation of CKD: Emerging Biomarkers PCSK9, EPHX2, AOPPs, and TBARSs.Life (Basel, Switzerland) · 2025Review
- PCSK9 in Vascular Aging and Age-Related Diseases.Aging and disease · 2025Review
- PCSK9 Enhances Cardiac Fibrogenesis via the Activation of Toll-like Receptor and NLRP3 Inflammasome Signaling.International journal of molecular sciences · 2025Article
- Cholesterol and Cholesterol-Lowering Medications in COVID-19-An Unresolved Matter.International journal of molecular sciences · 2024Review
- The Pleiotropic Effects of Lipid-Modifying Interventions: Exploring Traditional and Emerging Hypolipidemic Therapies.Metabolites · 2024Review
- Effects of PCSK9 on thrombosis and haemostasis in a variety of metabolic states: Lipids and beyond (Review).International journal of molecular medicine · 2024Review
- Proprotein convertase subtilisin/kexin 9 inhibitor downregulates microRNA-130a-3p expression in hepatocytes to alleviates atherosclerosis progression.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Review
- Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proprotein convertase subtilisin kexin 9 (PCSK9) increases LDL cholesterol (C) concentration by accelerating the hepatic degradation of the LDL receptor (R) thus promoting atherogenesis. The molecule, however, also exerts proinflammatory effects independent of circulating LDL-C by enhancing local cytokine production and activation of NFkB, a process that might involve Toll-like receptor 4 (TLR4), a crucial component of the innate immunity system. Tissue factor (TF), a glycoprotein which plays an essential role in coagulation and inflammation, is rapidly induced by circulating monocytes stimulated by proinflammatory agents through NFkB-dependent mechanisms. The aims of our study were (1) to assess whether PCSK9 may induce monocytic TF expression and (2) to evaluate whether the TLR4/NFkB signaling pathway may contribute to that effect. Experiments were carried out in peripheral blood mononuclear cells (PBMCs), THP-1 cells, and HEK293 cells transfected with plasmids encoding the human TLR4 complex. PCSK9 increased procoagulant activity (PCA), mRNA and TF protein expression in both PBMCs and THP-1 cultures. Pre-treatment with inhibitors of TLR4/NFkB signaling such as LPS-RS, CLI-095, and BAY 11-7082, downregulated PCSK9-induced TF expression. A similar effect was obtained by incubating cell cultures with anti-PCSK9 human monoclonal antibody. In TLR4-HEK293 cells, PCSK9 activated the TLR4/NFkB signaling pathway to an extent comparable to LPS, the specific agonist of TLR4s and quantitative confocal microscopy documented the colocalization of PCSK9 and TLR4s. In conclusion, PCSK9 induces TF expression through activation of TLR4/NFkB signaling.
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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.