ArticleThe Journal of clinical investigation2019
Lineage-specific events underlie aortic root aneurysm pathogenesis in Loeys-Dietz syndrome.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
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Who cites it
78 citing papers in PubMed, 116 citations in OpenAlex.
- Preclinical modeling of Loeys-Dietz syndrome: insights into mechanisms and therapy.Orphanet journal of rare diseases · 2026Review
- Mechanotransduction in Marfan Syndrome and Related Aortic Disorders: Insights from Transcriptomic Analyses.Genes · 2026Review
- Structural and Signaling Mechanisms of Aortic Wall Failure in Heritable Thoracic Aortic Disease.Cells · 2026Review
- Focal adhesion proteins confer smooth muscle anoikis resistance and protection against aortic aneurysm and dissection.JCI insight · 2026Article
- Advanced technologies of artery-on-a-chip: a review of construction strategies and disease models.Angiogenesis · 2026Review
- A cell and transcriptome atlas of human arterial vasculature.Cell genomics · 2025Article
- Phenotypic Switching of VSMCs in the Development of CVDs: Focus on miRs.International journal of molecular sciences · 2025Review
- Region-specific gene expression and sex inform about disease susceptibility in the aorta.Nature cardiovascular research · 2025Article
- Proximal aortic aneurysms in mice underexpressing transforming growth factor-β1.The journal of physiological sciences : JPS · 2025Article
- Smooth muscle cells and fibroblasts in the ascending aorta exhibit minor differences between embryonic origins in angiotensin II-driven transcriptional alterations.Scientific reports · 2025Article
- Chemokine (C-C Motif) Ligand 2 Expressing Adventitial Fibroblast Expansion During Loeys-Dietz Syndrome Aortic Aneurysm Formation.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Recommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Origins of Aortic Coarctation: A Vascular Smooth Muscle Compartment Boundary Model.Journal of developmental biology · 2025Article
- TGFBR3 dependent mechanism of TGFB2 in smooth muscle cell differentiation and implications for TGFB2-related aortic aneurysm.Stem cells translational medicine · 2025Article
- Single-Cell Transcriptomics Identifies Selective Lineage-Specific Regulation of Genes in Aortic Smooth Muscle Cells in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Heterogeneous Cardiac-Derived and Neural Crest-Derived Aortic Smooth Muscle Cells Exhibit Similar Transcriptional Changes After TGFβ Signaling Disruption.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Intrinsic GATA4 expression sensitizes the aortic root to dilation in a Loeys-Dietz syndrome mouse model.Nature cardiovascular research · 2024Article
- Identification of Genetic Variants Associated with Hereditary Thoracic Aortic Diseases (HTADs) Using Next Generation Sequencing (NGS) Technology and Genotype-Phenotype Correlations.International journal of molecular sciences · 2024Article
- Management of an elderly patient with nonsyndromicClinical case reports · 2024Article
- Coding and Non-Coding Transcriptomic Landscape of Aortic Complications in Marfan Syndrome.International journal of molecular sciences · 2024Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
The aortic root is the predominant site for development of aneurysm caused by heterozygous loss-of-function mutations in positive effectors of the transforming growth factor-β (TGF-β) pathway. Using a mouse model of Loeys-Dietz syndrome (LDS) that carries a heterozygous kinase-inactivating mutation in TGF-β receptor I, we found that the effects of this mutation depend on the lineage of origin of vascular smooth muscle cells (VSMCs). Secondary heart field-derived (SHF-derived), but not neighboring cardiac neural crest-derived (CNC-derived), VSMCs showed impaired Smad2/3 activation in response to TGF-β, increased expression of angiotensin II (AngII) type 1 receptor (Agtr1a), enhanced responsiveness to AngII, and higher expression of TGF-β ligands. The preserved TGF-β signaling potential in CNC-derived VSMCs associated, in vivo, with increased Smad2/3 phosphorylation. CNC-, but not SHF-specific, deletion of Smad2 preserved aortic wall architecture and reduced aortic dilation in this mouse model of LDS. Taken together, these data suggest that aortic root aneurysm predisposition in this LDS mouse model depends both on defective Smad signaling in SHF-derived VSMCs and excessive Smad signaling in CNC-derived VSMCs. This work highlights the importance of considering the regional microenvironment and specifically lineage-dependent variation in the vulnerability to mutations in the development and testing of pathogenic models for aortic aneurysm.
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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.