ArticleArteriosclerosis, thrombosis, and vascular biology2020
PKC (Protein Kinase C)-δ Modulates AT (Antithrombin) Signaling in Vascular Endothelial Cells.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Identifying dynamic antithrombin Ⅲ trajectories to predict clinical outcomes in intra-abdominal sepsis.Journal of intensive medicine · 2026Article
- Association of the p.Phe155del mutation in SERPINC1 with changed antithrombin function and increased risk of venous thromboembolism: clinical and functional observations.Thrombosis journal · 2025Article
- Physiological significance of antithrombin D-helix interaction with vascular GAGs.Blood advances · 2025Article
- Protein kinase C and endothelial dysfunction in select vascular diseases.Frontiers in cardiovascular medicine · 2025Review
- Mutual Inhibition of Antithrombin III and SARS-CoV-2 Cellular Attachment to Syndecans: Implications for COVID-19 Treatment and Vaccination.International journal of molecular sciences · 2024Article
- Hemostasis and endothelial functionality: the double face of coagulation factors.Haematologica · 2024Review
- Thrombomodulin Switches Signaling and Protease-Activated Receptor 1 Cleavage Specificity of Thrombin.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Thrombomodulin Regulates PTEN/AKT Signaling Axis in Endothelial Cells.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- PKCδ regulates the vascular biology in diabetic atherosclerosis.Cell communication and signaling : CCS · 2023Review
- A reduction of Syndecan-4 in macrophages promotes atherosclerosis by aggravating the proinflammatory capacity of macrophages.Journal of translational medicine · 2022Article
- Antithrombin protects against Plasmodium falciparum histidine-rich protein II-mediated inflammation and coagulation.Blood advances · 2022Article
- Extracellular Histones Bind Vascular Glycosaminoglycans and Inhibit the Anti-Inflammatory Function of Antithrombin.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Article
- Anticoagulant and signaling functions of antithrombin.Journal of thrombosis and haemostasis : JTH · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
objectiveNative and latent conformers of AT (antithrombin) induce anti-inflammatory and proapoptotic signaling activities, respectively, in vascular endothelial cells by unknown mechanisms. Synd-4 (syndecan-4) has been identified as a receptor that is involved in transmitting signaling activities of AT in endothelial cells. Approach and Results: In this study, we used flow cytometry, signaling assays, immunoblotting and confocal immunofluorescence microscopy to investigate the mechanism of the paradoxical signaling activities of high-affinity heparin (native) and low-affinity heparin (latent) conformers of AT in endothelial cells. We discovered that native AT binds to glycosaminoglycans on vascular endothelial cells via its heparin-binding D-helix to induce anti-inflammatory signaling responses by recruiting PKC (protein kinase C)-δ to the plasma membrane and promoting phosphorylation of the Synd-4 cytoplasmic domain at Ser179. By contrast, the binding of latent AT to endothelial cells to a site(s), which is not competed by the native AT, induces a proapoptotic effect by localizing PKC-δ to the perinuclear/nuclear compartment in endothelial cells. Overexpression of a dominant-negative form of PKC-δ resulted in inhibition of anti-inflammatory and proapoptotic signaling activities of both native and latent AT.
conclusionsThese results indicate that the native and latent conformers of AT may exert their distinct intracellular signaling effects through differentially modulating the subcellular localization of PKC-δ in endothelial cells.
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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.