ArticleProceedings of the National Academy of Sciences of the United States of America2016
Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 3 of them syntheses that pooled it.
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Who cites it
113 citing papers in PubMed, 3 syntheses or guidelines pooled it, 180 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
- Guideline
- 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
- Lysyl oxidase inhibition disrupts mitochondrial homeostasis to create vulnerability to ferroptosis in TNBC.Cell reports. Medicine · 2026Article
- Review
- Mechanics and mechanobiology of arterial development.Biomechanics and modeling in mechanobiology · 2026Review
- Functions of prolyl hydroxylation in elastin.The Journal of biological chemistry · 2026Article
- A Marfan-Associated FBN1 Nonsense Mutation Mouse Model Reveals Adventitial Inflammation During Aneurysm Progression.bioRxiv : the preprint server for biology · 2025Article
- Hypertriglyceridemia as a Key Contributor to Abdominal Aortic Aneurysm Development and Rupture: Insights From Genetic and Experimental Models.Circulation · 2025Article
- Oxidative DNA damage promotes vascular ageing associated with changes in extracellular matrix-regulating proteins.Cardiovascular research · 2025Article
- Extracellular matrix in vascular homeostasis and disease.Nature reviews. Cardiology · 2025Review
- Recommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Mechanisms of aortic dissection: From pathological changes to experimental andProgress in materials science · 2025Article
- Novel Insights into the Aortic Mechanical Properties of Mice Modeling Hereditary Aortic Diseases.Thrombosis and haemostasis · 2025Article
- Coordination among cytoskeletal organization, cell contraction, and extracellular matrix development is dependent on LOX for aneurysm prevention.The FEBS journal · 2025Article
- Modeling Thoracic Aortic Dissection Using Patient-Specific iPSCs Reveals VSMC Dysfunction and Extracellular Matrix Dysregulation.Stem cells international · 2025Article
- Transcriptional regulation of postnatal aortic development.Cells & development · 2024Article
- In Search of Mouse Models for Exfoliation Syndrome.American journal of ophthalmology · 2024Article
- LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- β-Aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Mice.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Thoracic aortic aneurysms and dissections (TAAD) represent a substantial cause of morbidity and mortality worldwide. Many individuals presenting with an inherited form of TAAD do not have causal mutations in the set of genes known to underlie disease. Using whole-genome sequencing in two first cousins with TAAD, we identified a missense mutation in the lysyl oxidase (LOX) gene (c.893T > G encoding p.Met298Arg) that cosegregated with disease in the family. Using clustered regularly interspaced short palindromic repeats (CRISPR)/clustered regularly interspaced short palindromic repeats-associated protein-9 nuclease (Cas9) genome engineering tools, we introduced the human mutation into the homologous position in the mouse genome, creating mice that were heterozygous and homozygous for the human allele. Mutant mice that were heterozygous for the human allele displayed disorganized ultrastructural properties of the aortic wall characterized by fragmented elastic lamellae, whereas mice homozygous for the human allele died shortly after parturition from ascending aortic aneurysm and spontaneous hemorrhage. These data suggest that a missense mutation in LOX is associated with aortic disease in humans, likely through insufficient cross-linking of elastin and collagen in the aortic wall. Mutation carriers may be predisposed to vascular diseases because of weakened vessel walls under stress conditions. LOX sequencing for clinical TAAD may identify additional mutation carriers in the future. Additional studies using our mouse model of LOX-associated TAAD have the potential to clarify the mechanism of disease and identify novel therapeutics specific to this genetic cause.
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