ArticleThe Journal of clinical investigation2014
Angiotensin II-dependent TGF-β signaling contributes to Loeys-Dietz syndrome vascular pathogenesis.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 5 of them syntheses that pooled it.
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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
171 citing papers in PubMed, 5 syntheses or guidelines pooled it, 246 citations in OpenAlex.
- 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.The Journal of thoracic and cardiovascular surgery · 2023Guideline
- 2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.Journal of the American College of Cardiology · 2022Guideline
- Guideline
- The Role of Transforming Growth Factor-β Signaling in Myxomatous Mitral Valve Degeneration.Frontiers in cardiovascular medicine · 2022Pooled it
- Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies-Statement From ATVB Council.Arteriosclerosis, thrombosis, and vascular biology · 2018Guideline
- Losartan Treatment Reduces Esophageal Eosinophilic Inflammation in a Subset of Eosinophilic Esophagitis.The journal of allergy and clinical immunology. In practice · 2024Trial
- Mouse Models of Aortic Pathologies: Deciphering Molecular and Cellular Mechanisms from Bench to Bedside.CJC open · 2026Review
- Genetic and molecular mechanisms of hereditary thoracic aortic aneurysm and dissection (Review).Molecular medicine reports · 2026Review
- A Preliminary Zebrafish Model ofGenes · 2026Article
- Development of a zebrafish model of Loeys-Dietz syndrome through tgfbr2b knockdown.Journal of human genetics · 2026Article
- Preclinical modeling of Loeys-Dietz syndrome: insights into mechanisms and therapy.Orphanet journal of rare diseases · 2026Review
- Structural and Signaling Mechanisms of Aortic Wall Failure in Heritable Thoracic Aortic Disease.Cells · 2026Review
- Impaired Remodeling of Tight Junctions Associated with Loss of Enamel Rod Decussation in Tgfbr2Calcified tissue international · 2026Article
- Associations Between MicroRNA and Abdominal Aortic Aneurysm Diameter Differ by Sex.Biomedicines · 2026Article
- Variability, asymmetry and sexual dimorphism in craniofacial anomalies in Loeys-Dietz syndrome 2: geometric morphometric analysis in mice.Scientific reports · 2026Article
- Review
- Ischemic stroke as an initial manifestation of Loeys-Dietz syndrome type 3 caused by the recurrent p.Arg287Trp variant inFrontiers in genetics · 2026Article
- Perivascular inflammation in the progression of aortic aneurysms in Marfan syndrome.JCI insight · 2025Article
- Global, regional, and national burden of aortic aneurysm disease and its attributable risk factor, 1990-2021: a systematic analysis for the global burden of disease study 2021.Internal and emergency medicine · 2025Article
- Recommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
111 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is characterized by a high risk for aneurysm and dissection throughout the arterial tree and phenotypically resembles Marfan syndrome. LDS is caused by heterozygous missense mutations in either TGF-β receptor gene (TGFBR1 or TGFBR2), which are predicted to result in diminished TGF-β signaling; however, aortic surgical samples from patients show evidence of paradoxically increased TGF-β signaling. We generated 2 knockin mouse strains with LDS mutations in either Tgfbr1 or Tgfbr2 and a transgenic mouse overexpressing mutant Tgfbr2. Knockin and transgenic mice, but not haploinsufficient animals, recapitulated the LDS phenotype. While heterozygous mutant cells had diminished signaling in response to exogenous TGF-β in vitro, they maintained normal levels of Smad2 phosphorylation under steady-state culture conditions, suggesting a chronic compensation. Analysis of TGF-β signaling in the aortic wall in vivo revealed progressive upregulation of Smad2 phosphorylation and TGF-β target gene output, which paralleled worsening of aneurysm pathology and coincided with upregulation of TGF-β1 ligand expression. Importantly, suppression of Smad2 phosphorylation and TGF-β1 expression correlated with the therapeutic efficacy of the angiotensin II type 1 receptor antagonist losartan. Together, these data suggest that increased TGF-β signaling contributes to postnatal aneurysm progression in LDS.
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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.