ArticleThe Journal of clinical investigation2016
FOXE3 mutations predispose to thoracic aortic aneurysms and dissections.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01322165 (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions), which is not on this map. Cited by 51 papers, 2 of them syntheses that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 96 citations in OpenAlex.
- Systematic Review of Studies That Have Evaluated Screening Tests in Relatives of Patients Affected by Nonsyndromic Thoracic Aortic Disease.Journal of the American Heart Association · 2018Pooled it
- Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies-Statement From ATVB Council.Arteriosclerosis, thrombosis, and vascular biology · 2018Guideline
- Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms.Scientific reports · 2019Trial
- Recommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Modeling thoracic aortic genetic variants in the zebrafish: useful for predicting clinical pathogenicity?Frontiers in cardiovascular medicine · 2025Review
- Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms.Progress in retinal and eye research · 2024Review
- Heritable thoracic aortic disease: a literature review on genetic aortopathies and current surgical management.General thoracic and cardiovascular surgery · 2024Review
- Current understanding of the genetics of thoracic aortic disease.Vessel plus · 2024Article
- Developmental endothelial locus 1: the present and future of an endogenous factor in vessels.Frontiers in physiology · 2024Review
- Inducing aortic aneurysm/dissection in zebrafish: evaluating the efficacy of β-Aminopropionic Nitrile as a model.Animal cells and systems · 2024Article
- Causal effect of hypertension and blood pressure on aortic diseases: evidence from Mendelian randomization.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Article
- Tracking an Elusive Killer: State of the Art of Molecular-Genetic Knowledge and Laboratory Role in Diagnosis and Risk Stratification of Thoracic Aortic Aneurysm and Dissection.Diagnostics (Basel, Switzerland) · 2022Review
- MED12 Regulates Smooth Muscle Cell Functions and Participates in the Development of Aortic Dissection.Genes · 2022Article
- The role of vascular smooth muscle cells in the development of aortic aneurysms and dissections.European journal of clinical investigation · 2022Review
- The ascending aorta of male hypertensive bicuspid aortic valve patients preferentially associated with a cellular aneurysmal phenotype.Physiological reports · 2022Article
- Arterial dissections: Common features and new perspectives.Frontiers in cardiovascular medicine · 2022Review
- Targeting Ferroptosis as a Novel Approach to Alleviate Aortic Dissection.International journal of biological sciences · 2022Article
- Identification of pathological-related and diagnostic potential circular RNAs in Stanford type A aortic dissection.Frontiers in cardiovascular medicine · 2022Article
- Evaluating the monogenic contribution and genotype-phenotype correlation in patients with isolated thoracic aortic aneurysm.European journal of human genetics : EJHG · 2021Article
- Review
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
Abstract
The ascending thoracic aorta is designed to withstand biomechanical forces from pulsatile blood. Thoracic aortic aneurysms and acute aortic dissections (TAADs) occur as a result of genetically triggered defects in aortic structure and a dysfunctional response to these forces. Here, we describe mutations in the forkhead transcription factor FOXE3 that predispose mutation-bearing individuals to TAAD. We performed exome sequencing of a large family with multiple members with TAADs and identified a rare variant in FOXE3 with an altered amino acid in the DNA-binding domain (p.Asp153His) that segregated with disease in this family. Additional pathogenic FOXE3 variants were identified in unrelated TAAD families. In mice, Foxe3 deficiency reduced smooth muscle cell (SMC) density and impaired SMC differentiation in the ascending aorta. Foxe3 expression was induced in aortic SMCs after transverse aortic constriction, and Foxe3 deficiency increased SMC apoptosis and ascending aortic rupture with increased aortic pressure. These phenotypes were rescued by inhibiting p53 activity, either by administration of a p53 inhibitor (pifithrin-α), or by crossing Foxe3-/- mice with p53-/- mice. Our data demonstrate that FOXE3 mutations lead to a reduced number of aortic SMCs during development and increased SMC apoptosis in the ascending aorta in response to increased biomechanical forces, thus defining an additional molecular pathway that leads to familial thoracic aortic disease.
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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.