ArticleArteriosclerosis, thrombosis, and vascular biology2015
Macrophage Notch Ligand Delta-Like 4 Promotes Vein Graft Lesion Development: Implications for the Treatment of Vein Graft Failure.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers.
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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.
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Who cites it
43 citing papers in PubMed.
- Review
- Monocyte Dll4 Contributes to Systemic Inflammation in People Living With HIV.Circulation research · 2026Article
- Precision engineering of macrophage reprogramming with RNA interference-loaded lipid nanoparticles: a game-changer in cancer immunotherapy.Drug delivery and translational research · 2026Review
- The Blockade of Delta-Like Ligand 1 Inhibits Atherosclerotic Lesion Formation and Attenuates Plaque Vulnerability.Journal of atherosclerosis and thrombosis · 2026Article
- Ligand-Specific Notch Signaling in Atherosclerosis: Implications for Inflammation and Plaque Stability.Journal of atherosclerosis and thrombosis · 2026Article
- Nanomedicine-based strategies for the treatment of vein graft disease.Nature reviews. Cardiology · 2025Review
- Gene expression profiles of precursor cells identify compounds that reduce NRP1 surface expression in macrophages: Implication for drug repositioning for COVID-19.Frontiers in cardiovascular medicine · 2024Article
- Delta- like ligand 4- expressing macrophages and human diseases: Insights into pathophysiology and therapeutic opportunities.Heliyon · 2023Review
- New insights into maladaptive vascular responses to donor specific HLA antibodies in organ transplantation.Frontiers in transplantation · 2023Review
- Substituting racemic ionizable lipids with stereopure ionizable lipids can increase mRNA delivery.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) Promotes Macrophage Activation via LDL Receptor-Independent Mechanisms.Circulation research · 2022Article
- Nanoparticle-Mediated Delivery of Pitavastatin to Monocytes/Macrophages Inhibits Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in ApoeJournal of atherosclerosis and thrombosis · 2022Article
- Nanoparticle-Based RNAi Therapeutics Targeting Cancer Stem Cells: Update and Prospective.Pharmaceutics · 2021Review
- PD-L1 (Programmed Death Ligand 1) Regulates T-Cell Differentiation to Control Adaptive Venous Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Article
- The Role of Immunomodulation in Vein Graft Remodeling and Failure.Journal of cardiovascular translational research · 2021Review
- Notch Signaling Ligand Jagged1 Enhances Macrophage-Mediated Response toFrontiers in microbiology · 2021Article
- Notch in mechanotransduction - from molecular mechanosensitivity to tissue mechanostasis.Journal of cell science · 2020Review
- S100A9-RAGE Axis Accelerates Formation of Macrophage-Mediated Extracellular Vesicle Microcalcification in Diabetes Mellitus.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Distinct subsets of T cells and macrophages impact venous remodeling during arteriovenous fistula maturation.JVS-vascular science · 2020Article
Corrections and comments
- Erratum issuedCorrection.2016
Authors and funding
14 authors.
Funding
Abstract
objectiveDespite its large clinical impact, the underlying mechanisms for vein graft failure remain obscure and no effective therapeutic solutions are available. We tested the hypothesis that Notch signaling promotes vein graft disease. APPROACH AND
resultsWe used 2 biotherapeutics for Delta-like ligand 4 (Dll4), a Notch ligand: (1) blocking antibody and (2) macrophage- or endothelial cell (EC)-targeted small-interfering RNA. Dll4 antibody administration for 28 days inhibited vein graft lesion development in low-density lipoprotein (LDL) receptor-deficient (Ldlr(-/-)) mice, and suppressed macrophage accumulation and macrophage expression of proinflammatory M1 genes. Dll4 antibody treatment for 7 days after grafting also reduced macrophage burden at day 28. Dll4 silencing via macrophage-targeted lipid nanoparticles reduced lesion development and macrophage accumulation, whereas EC-targeted Dll4 small-interfering RNA produced no effects. Gain-of-function and loss-of-function studies suggested in vitro that Dll4 induces proinflammatory molecules in macrophages. Macrophage Dll4 also stimulated smooth muscle cell proliferation and migration and suppressed their differentiation.
conclusionsThese results suggest that macrophage Dll4 promotes lesion development in vein grafts via macrophage activation and crosstalk between macrophages and smooth muscle cells, supporting the Dll4-Notch axis as a novel therapeutic target.
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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.