ArticleJournal of vascular surgery2015
Differential expression of Hedgehog/Notch and transforming growth factor-β in human abdominal aortic aneurysms.
Article in Journal of vascular surgery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Therapeutic Targeting of Signaling Pathways in Abdominal Aortic Aneurysm: From Pathogenesis to Precision Medicine.Drug design, development and therapy · 2025Review
- Olfactory Receptors and Aortic Aneurysm: Review of Disease Pathways.Journal of clinical medicine · 2024Review
- O304 alleviates abdominal aortic aneurysm formation via AMPK/mTOR/MMP pathway activation.Frontiers in pharmacology · 2024Article
- The mechanism and therapy of aortic aneurysms.Signal transduction and targeted therapy · 2023Review
- The role of long non-coding RNA in abdominal aortic aneurysm.Frontiers in genetics · 2023Review
- Identification of Novel Plasma Biomarkers for Abdominal Aortic Aneurysm by Protein Array Analysis.Biomolecules · 2022Article
- Fibromuscular Dysplasia and Abdominal Aortic Aneurysms Are Dimorphic Sex-Specific Diseases With Shared Complex Genetic Architecture.Circulation. Genomic and precision medicine · 2022Article
- The role of vascular smooth muscle cells in the development of aortic aneurysms and dissections.European journal of clinical investigation · 2022Review
- Adventitial Fibroblasts in Aortic Aneurysm: Unraveling Pathogenic Contributions to Vascular Disease.Diagnostics (Basel, Switzerland) · 2022Review
- RUNX3 is up-regulated in abdominal aortic aneurysm and regulates the function of vascular smooth muscle cells by regulating TGF-β1.Journal of molecular histology · 2022Article
- Critical Roles of Balanced T Helper 9 Cells and Regulatory T Cells in Allergic Airway Inflammation and Tumor Immunity.Journal of immunology research · 2021Review
- Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm.International journal of molecular sciences · 2020Review
- Divergent effects of canonical and non-canonical TGF-β signalling on mixed contractile-synthetic smooth muscle cell phenotype in human Marfan syndrome aortic root aneurysms.Journal of cellular and molecular medicine · 2020Article
- Mechanisms underlying the inhibitory effects of probucol on elastase-induced abdominal aortic aneurysm in mice.British journal of pharmacology · 2020Article
- Role of Hedgehog Signaling in Vasculature Development, Differentiation, and Maintenance.International journal of molecular sciences · 2019Review
- Updates of Recent Aortic Aneurysm Research.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway.Oxidative medicine and cellular longevity · 2019Review
- The genetics and biomechanics of thoracic aortic diseases.Vascular biology (Bristol, England) · 2019Review
- Targeting the Notch1 oncogene by miR-139-5p inhibits glioma metastasis and epithelial-mesenchymal transition (EMT).BMC neurology · 2018Article
- TGF-β (Transforming Growth Factor-β) Signaling Protects the Thoracic and Abdominal Aorta From Angiotensin II-Induced Pathology by Distinct Mechanisms.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveThe molecular mechanisms leading to the development of abdominal aortic aneurysms (AAAs) remain poorly understood. The aim of this study was to determine the expression of Sonic Hedgehog (SHh), transforming growth factor β (TGF-β), and Notch signaling components in human aneurysmal and nonaneurysmal aorta in vivo.
methodsPaired tissue samples were obtained from aneurysmal and nonaneurysmal (control) segments of the aortic wall of eight patients with suitable anatomy undergoing open repair of infrarenal AAAs. Protein and messenger RNA (mRNA) expression levels were determined by Western blot and quantitative real-time polymerase chain reaction analysis.
resultsAneurysm development resulted in a significant reduction in vascular smooth muscle (vSMC) differentiation genes α-actin and SMC22α at both mRNA and protein levels. In parallel experiments, an 80.0% ± 15% reduction in SHh protein expression was observed in aneurysmal tissue compared with control. SHh and Ptc-1 mRNA levels were also significantly decreased, by 82.0% ± 10% and 75.0% ± 5%, respectively, in aneurysmal tissue compared with nonaneurysmal control tissue. Similarly, there was a 50.0% ± 9% and 60.0% ± 4% reduction in Notch receptor 1 intracellular domain and Hrt-2 protein expression, respectively, in addition to significant reductions in Notch 1, Notch ligand Delta like 4, and Hrt-2 mRNA expression in aneurysmal tissue compared with nonaneurysmal tissue. There was no change in Hrt-1 expression observed in aneurysmal tissue compared with control. In parallel experiments, we found a 2.2 ± 0.2-fold and a 5.6 ± 2.2-fold increase in TGF-β mRNA and protein expression, respectively, in aneurysmal tissue compared with nonaneurysmal tissue. In vitro, Hedgehog signaling inhibition with cyclopamine in human aortic SMCs resulted in decreased Hedgehog/Notch signaling component and vSMC differentiation gene expression. Moreover, cyclopamine significantly increased TGF-β1 mRNA expression by 2.6 ± 0.9-fold.
conclusionsThese results suggest that SHh/Notch and TGF-β signaling are differentially regulated in aneurysmal tissue compared with nonaneurysmal tissue. Changes in these signaling pathways and the resulting changes in vSMC content may play a causative role in the development of AAAs.
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