ArticleCirculation research2010
Fibulin-4 deficiency results in ascending aortic aneurysms: a potential link between abnormal smooth muscle cell phenotype and aneurysm progression.
Article in Circulation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
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Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 163 citations in OpenAlex.
- Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies-Statement From ATVB Council.Arteriosclerosis, thrombosis, and vascular biology · 2018Guideline
- ATP7A-fibulin-4 complex delivers copper in the Golgi to activate LOX in renal fibrosis.JCI insight · 2026Article
- ECM formation and degradation during fibrosis, repair, and regeneration.npj metabolic health and disease · 2025Review
- Recommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Sexual dimorphism in the downregulation of extracellular matrix genes contributes to aortic stiffness in female mice.American journal of physiology. Heart and circulatory physiology · 2025Article
- Novel Insights into the Aortic Mechanical Properties of Mice Modeling Hereditary Aortic Diseases.Thrombosis and haemostasis · 2025Article
- Transcriptional regulation of postnatal aortic development.Cells & development · 2024Article
- Distinct Patterns of Smooth Muscle Phenotypic Modulation in Thoracic and Abdominal Aortic Aneurysms.Journal of cardiovascular development and disease · 2024Article
- The mitochondrial protease ClpP is a druggable target that controls VSMC phenotype by a SIRT1-dependent mechanism.Redox biology · 2024Article
- Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm.International journal of molecular sciences · 2024Review
- TheFrontiers in cardiovascular medicine · 2024Article
- Case Report and literature review: Delayed diagnosis of ARCL1B due to a newly reported homozygous mutation c.464A>C p. (Tyr155Ser) in theFrontiers in genetics · 2024Article
- FBLN7 mediates vascular smooth muscle cell phenotype switching and vascular remodeling in hypertension.Theranostics · 2024Article
- The matrix reloaded - Addressing structural integrity of the aortic wall in aneurysmal disease.Biomaterials and biosystems · 2023Article
- Protective Role of Endothelial Fibulin-4 in Valvulo-Arterial Integrity.Journal of the American Heart Association · 2023Article
- G2Φnet: Relating genotype and biomechanical phenotype of tissues with deep learning.PLoS computational biology · 2022Article
- Experimental and Mouse-Specific Computational Models of the Fbln4Cardiovascular engineering and technology · 2022Article
- The role of vascular smooth muscle cells in the development of aortic aneurysms and dissections.European journal of clinical investigation · 2022Review
- Epigallocatechin gallate facilitates extracellular elastin fiber formation in induced pluripotent stem cell derived vascular smooth muscle cells for tissue engineering.Journal of molecular and cellular cardiology · 2022Article
- Molecular Imaging of Aortic Aneurysm and Its Translational Power for Clinical Risk Assessment.Frontiers in medicine · 2022Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
rationaleLoss of fibulin-4 during embryogenesis results in perinatal lethality because of aneurysm rupture, and defective elastic fiber assembly has been proposed as an underlying cause for the aneurysm phenotype. However, aneurysms are never seen in mice deficient for elastin, or for fibulin-5, which absence also leads to compromised elastic fibers.
objectiveWe sought to determine the mechanism of aneurysm development in the absence of fibulin-4 and establish the role of fibulin-4 in aortic development. METHODS AND
resultsWe generated germline and smooth muscle cell (SMC)-specific deletion of the fibulin-4 gene in mice (Fbln4(GKO) and Fbln4(SMKO), respectively). Fbln4(GKO) and Fbln4(SMKO) aortic walls fail to fully differentiate, exhibiting reduced expression of SM-specific contractile genes and focal proliferation of SMCs accompanied by degenerative changes of the medial wall. Marked upregulation of extracellular signal-regulated kinase 1/2 signaling pathway was observed in the aneurysmal wall of Fbln4(GKO) and Fbln4(SMKO) mice and both mutants developed aneurysm predominantly in the ascending thoracic aorta. In vitro, Fbln4(GKO) SMCs exhibit an immature SMC phenotype with a marked reduction of SM-myosin heavy chain and increased proliferative capacity.
conclusionsThe vascular phenotype in Fbln4 mutant mice is remarkably similar to a subset of human thoracic aortic aneurysms caused by mutations in SMC contractile genes. Our study provides a potential link between the intrinsic properties of SMCs and aneurysm progression in vivo and supports the dual role of fibulin-4 in the formation of elastic fibers as well as terminal differentiation and maturation of SMCs in the aortic 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.