ArticleJCI insight2019
Intracellular retention of mutant lysyl oxidase leads to aortic dilation in response to increased hemodynamic stress.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Iron, Copper, and Zinc Dyshomeostasis in Cardiovascular and Cerebrovascular Diseases: Redox Mechanisms, Evidence Levels, and Translational Prospects.International journal of molecular sciences · 2026Review
- Heritable Thoracic Aortic Diseases in Pediatric Practice: From Molecular Mechanisms to Genotype-Informed Management, a Comprehensive Narrative Review.Journal of clinical medicine · 2026Review
- Structural and Signaling Mechanisms of Aortic Wall Failure in Heritable Thoracic Aortic Disease.Cells · 2026Review
- Structural and transcriptomic alterations underlying the progression of aortic dissection in Fbn1Scientific reports · 2026Article
- Oxidative Stress-Induced DNA Damage Response Pathways in Aortic Disease: Implications for Inflammation and Vascular Degeneration.International journal of molecular sciences · 2026Review
- Short-term disruption of TGF-β signaling in adult mice renders the aorta vulnerable to hypertension-induced dissection.JCI insight · 2025Article
- Coordination among cytoskeletal organization, cell contraction, and extracellular matrix development is dependent on LOX for aneurysm prevention.The FEBS journal · 2025Article
- Sex differences and role of lysyl oxidase-like 2 in angiotensin II-induced hypertension in mice.American journal of physiology. Heart and circulatory physiology · 2024Article
- Changes in transmural mass transport correlate with ascending thoracic aortic aneurysm diameter in a fibulin-4 E57K knockin mouse model.American journal of physiology. Heart and circulatory physiology · 2023Article
- PRDM16 deficiency in vascular smooth muscle cells aggravates abdominal aortic aneurysm.JCI insight · 2023Article
- Mechanistic insight into lysyl oxidase in vascular remodeling and angiogenesis.Genes & diseases · 2023Review
- Increases in hydraulic conductance and solute permeability in a mouse model of ascending thoracic aortic aneurysm.Journal of biomechanics · 2022Article
- Copper-Binding Domain Variation in a Novel Murine Lysyl Oxidase Model Produces Structurally Inferior Aortic Elastic Fibers Whose Failure Is Modified by Age, Sex, and Blood Pressure.International journal of molecular sciences · 2022Article
- The Expression Patterns and Roles of Lysyl Oxidases in Aortic Dissection.Frontiers in cardiovascular medicine · 2021Article
- Chemokine mediated signalling within arteries promotes vascular smooth muscle cell recruitment.Communications biology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Heterozygous missense mutations in lysyl oxidase (LOX) are associated with thoracic aortic aneurysms and dissections. To assess how LOX mutations modify protein function and lead to aortic disease, we studied the factors that influence the onset and progression of vascular aneurysms in mice bearing a Lox mutation (p.M292R) linked to aortic dilation in humans. We show that mice heterozygous for the M292R mutation did not develop aneurysmal disease unless challenged with increased hemodynamic stress. Vessel dilation was confined to the ascending aorta although both the ascending and descending aortae showed changes in vessel wall structure, smooth muscle cell number and inflammatory cell recruitment that differed between wild-type and mutant animals. Studies with isolated cells found that M292R-mutant Lox is retained in the endoplasmic reticulum and ultimately cleared through an autophagy/proteasome pathway. Because the mutant protein does not transit to the Golgi where copper incorporation occurs, the protein is never catalytically active. These studies show that the M292R mutation results in LOX loss-of-function due to a secretion defect that predisposes the ascending aorta in mice (and by extension humans with similar mutations) to arterial dilation when exposed to risk factors that impart stress to the arterial wall.
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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.