ArticleProceedings of the National Academy of Sciences of the United States of America2012
Notch ligand delta-like 4 blockade attenuates atherosclerosis and metabolic disorders.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed.
- Review
- Pretreatment With BTK Inhibitors Improved the Sensitivity of DLBCL Cells to CAR-T Cells in a Coculture System by Downregulating the Polarisation of M2 Macrophages.Journal of cellular and molecular medicine · 2026Article
- Monocyte Dll4 Contributes to Systemic Inflammation in People Living With HIV.Circulation research · 2026Article
- Ligand-Specific Notch Signaling in Atherosclerosis: Implications for Inflammation and Plaque Stability.Journal of atherosclerosis and thrombosis · 2026Article
- The Blockade of Delta-Like Ligand 1 Inhibits Atherosclerotic Lesion Formation and Attenuates Plaque Vulnerability.Journal of atherosclerosis and thrombosis · 2026Article
- Systematic monocyte subset analysis reveals differential contribution of Notch signaling components to monocyte heterogeneity.iScience · 2025Article
- Multifaceted Role of Notch Signaling in Vascular Health and Diseases.Biomedicines · 2025Review
- The Role of Notch Signaling and Gut Microbiota in Autoinflammatory Diseases: Mechanisms and Future Views.Biomedicines · 2025Review
- Macrophages: friend or foe in diabetes pathogenesis and therapy.Frontiers in immunology · 2025Review
- CADASIL orFrontiers in neurology · 2025Review
- Vascular inflammation in chronic kidney disease: the role of uremic toxins in macrophage activation.Frontiers in cardiovascular medicine · 2025Review
- Adipose tissue-selective ablation of ADAM10 results in divergent metabolic phenotypes following long-term dietary manipulation.Adipocyte · 2024Article
- Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification.The EMBO journal · 2024Article
- Research progress of Ganoderma lucidum polysaccharide in prevention and treatment of Atherosclerosis.Heliyon · 2024Review
- 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
- Obesity-associated Airway Hyperresponsiveness: Mechanisms Underlying Inflammatory Markers and Possible Pharmacological Interventions.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Delta- like ligand 4- expressing macrophages and human diseases: Insights into pathophysiology and therapeutic opportunities.Heliyon · 2023Review
- Small-Extracellular-Vesicle-Derived miRNA Profile Identifies miR-483-3p and miR-326 as Regulators in the Pathogenesis of Antiphospholipid Syndrome (APS).International journal of molecular sciences · 2023Article
- TAOK3 limits age-associated inflammation by negatively modulating macrophage differentiation and their production of TNFα.Immunity & ageing : I & A · 2023Article
- Selective inhibitors of the PSEN1-gamma-secretase complex.The Journal of biological chemistry · 2023Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors.
Funding
Abstract
Atherosclerosis and insulin resistance are major components of the cardiometabolic syndrome, a global health threat associated with a systemic inflammatory state. Notch signaling regulates tissue development and participates in innate and adaptive immunity in adults. The role of Notch signaling in cardiometabolic inflammation, however, remains obscure. We noted that a high-fat, high-cholesterol diet increased expression of the Notch ligand Delta-like 4 (Dll4) in atheromata and fat tissue in LDL-receptor-deficient mice. Blockade of Dll4-Notch signaling using neutralizing anti-Dll4 antibody attenuated the development of atherosclerosis, diminished plaque calcification, improved insulin resistance, and decreased fat accumulation. These changes were accompanied by decreased macrophage accumulation, diminished expression of monocyte chemoattractant protein-1 (MCP-1), and lower levels of nuclear factor-κB (NF-κB) activation. In vitro cell culture experiments revealed that Dll4-mediated Notch signaling increases MCP-1 expression via NF-κB, providing a possible mechanism for in vivo effects. Furthermore, Dll4 skewed macrophages toward a proinflammatory phenotype ("M1"). These results suggest that Dll4-Notch signaling plays a central role in the shared mechanism for the pathogenesis of cardiometabolic disorders.
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