ArticleJournal of the American Heart Association2014
Pharmacological inhibitor of notch signaling stabilizes the progression of small abdominal aortic aneurysm in a mouse model.
Article in Journal of the American Heart Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 56 citations in OpenAlex.
- The transcription factor RBPJ is required for inflammatory macrophage activation in thoracic aortic dissection by mediating mechanotransduction-induced glycolysis.Cellular and molecular life sciences : CMLS · 2025Article
- Myeloid Cells in Abdominal Aortic Aneurysm.Current atherosclerosis reports · 2025Review
- Therapeutic Targeting of Signaling Pathways in Abdominal Aortic Aneurysm: From Pathogenesis to Precision Medicine.Drug design, development and therapy · 2025Review
- Macrophage polarization and metabolic reprogramming in abdominal aortic aneurysm.Immunity, inflammation and disease · 2024Review
- Predicting feature genes correlated with immune infiltration in patients with abdominal aortic aneurysm based on machine learning algorithms.Scientific reports · 2024Article
- Nuclear mechanosensing of the aortic endothelium in health and disease.Disease models & mechanisms · 2023Review
- Long noncoding RNA TUG1 regulates smooth muscle cell differentiation via KLF4-myocardin axis.American journal of physiology. Cell physiology · 2023Article
- Endothelial cell senescence exacerbates pulmonary hypertension by inducing juxtacrine Notch signaling in smooth muscle cells.iScience · 2023Article
- Age as a risk factor in vasculitis.Seminars in immunopathology · 2022Review
- Gut microbiome sheds light on the development and treatment of abdominal aortic aneurysm.Frontiers in cardiovascular medicine · 2022Review
- Single-Cell Sequencing Analysis and Multiple Machine Learning Methods Identified G0S2 and HPSE as Novel Biomarkers for Abdominal Aortic Aneurysm.Frontiers in immunology · 2022Article
- Article
- Review
- Vinpocetine protects against the development of experimental abdominal aortic aneurysms.Clinical science (London, England : 1979) · 2020Article
- AT2R agonist NP-6A4 mitigates aortic stiffness and proteolytic activity in mouse model of aneurysm.Journal of cellular and molecular medicine · 2020Article
- Collagen fibril abnormalities in human and mice abdominal aortic aneurysm.Acta biomaterialia · 2020Article
- DAPT, a potent Notch inhibitor regresses actively growing abdominal aortic aneurysm via divergent pathways.Clinical science (London, England : 1979) · 2020Article
- COVID-19 in the heart and the lungs: could we "Notch" the inflammatory storm?Basic research in cardiology · 2020Article
- Oestrogen Receptor β Activation Protects Against Myocardial Infarction via Notch1 Signalling.Cardiovascular drugs and therapy · 2020Article
- Insight into the expression of toll-like receptors 2 and 4 in patients with abdominal aortic aneurysm.Molecular biology reports · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe progression of abdominal aortic aneurysm (AAA) involves a sustained influx of proinflammatory macrophages, which exacerbate tissue injury by releasing cytokines, chemokines, and matrix metalloproteinases. Previously, we showed that Notch deficiency reduces the development of AAA in the angiotensin II-induced mouse model by preventing infiltration of macrophages. Here, we examined whether Notch inhibition in this mouse model prevents progression of small AAA and whether these effects are associated with altered macrophage differentiation. METHODS AND
resultsTreatment with pharmacological Notch inhibitor (DAPT [N-(N-[3,5-difluorophenacetyl]-L-alanyl)-S-phenylglycine t-butyl ester]) at day 3 or 8 of angiotensin II infusion arrested the progression of AAA in Apoe(-/-) mice, as demonstrated by a decreased luminal diameter and aortic width. The abdominal aortas of Apoe(-/-) mice treated with DAPT showed decreased expression of matrix metalloproteinases and presence of elastin precursors including tropoelastin and hyaluronic acid. Marginal adventitial thickening observed in the aorta of DAPT-treated Apoe(-/-) mice was not associated with increased macrophage content, as observed in the mice treated with angiotensin II alone. Instead, DAPT-treated abdominal aortas showed increased expression of Cd206-positive M2 macrophages and decreased expression of Il12-positive M1 macrophages. Notch1 deficiency promoted M2 differentiation of macrophages by upregulating transforming growth factor β2 in bone marrow-derived macrophages at basal levels and in response to IL4. Protein expression of transforming growth factor β2 and its downstream effector pSmad2 also increased in DAPT-treated Apoe(-/-) mice, indicating a potential link between Notch and transforming growth factor β2 signaling in the M2 differentiation of macrophages.
conclusionsPharmacological inhibitor of Notch signaling prevents the progression of AAA by macrophage differentiation-dependent mechanisms. The study also provides insights for novel therapeutic strategies to prevent the progression of small AAA.
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