ArticleJCI insight2019
Systems pharmacology-based integration of human and mouse data for drug repurposing to treat thoracic aneurysms.
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 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- ADAR1 and ADAR2 Expression in the Thoracic Aortic Wall Correlates with Aneurysm Severity and Dissection Risk: Insights into A-to-I RNA Editing Dysregulation in Marfan Syndrome-Derived vSMCs.International journal of molecular sciences · 2026Article
- The aorta in Marfan syndrome: from molecular mechanisms to mechanobiological dysfunction.Cardiovascular research · 2026Review
- Mechanotransduction in Marfan Syndrome and Related Aortic Disorders: Insights from Transcriptomic Analyses.Genes · 2026Review
- Data-driven prioritization of mouse strains for improved preclinical modeling of rare and common disease.bioRxiv : the preprint server for biology · 2026Article
- Fibrillin-1 Deficiency Perturbs Aortic Cholinergic Relaxation and Adrenergic Contraction in a Mouse Model of Early Onset Progressively Severe Marfan Syndrome.Journal of vascular research · 2025Article
- Multiscale mapping of transcriptomic signatures for cardiotoxic drugs.Nature communications · 2024Article
- Analysis of Vascular Smooth Muscle Cells from Thoracic Aortic Aneurysms Reveals DNA Damage and Cell Cycle Arrest as Hallmarks in Bicuspid Aortic Valve Patients.Journal of proteome research · 2024Article
- Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm.International journal of molecular sciences · 2024Review
- Insights into elastic fiber fragmentation: Mechanisms and treatment of aortic aneurysm in Marfan syndrome.Vascular pharmacology · 2023Review
- Multi-omics in thoracic aortic aneurysm: the complex road to the simplification.Cell & bioscience · 2023Review
- FN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- A phenotypic screen of Marfan syndrome iPSC-derived vascular smooth muscle cells uncovers GSK3β as a new target.Stem cell reports · 2023Article
- A drug repurposing method based on inhibition effect on gene regulatory network.Computational and structural biotechnology journal · 2023Article
- Synaptojanin 1 Modulates Functional Recovery After Incomplete Spinal Cord Injury in Male Apolipoprotein E Epsilon 4 Mice.Neurotrauma reports · 2023Article
- Spinal cord injury regulates circular RNA expression in axons.Frontiers in molecular neuroscience · 2023Article
- Marfan syndrome.Nature reviews. Disease primers · 2021Review
- Inhibition of HIPK2 Alleviates Thoracic Aortic Disease in Mice With Progressively Severe Marfan Syndrome.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Connectivity Mapping Identifies BI-2536 as a Potential Drug to Treat Diabetic Kidney Disease.Diabetes · 2021Article
- An Overview of Investigational and Experimental Drug Treatment Strategies for Marfan Syndrome.Journal of experimental pharmacology · 2021Review
- The Human ApoE4 Variant Reduces Functional Recovery and Neuronal Sprouting After Incomplete Spinal Cord Injury in Male Mice.Frontiers in cellular neuroscience · 2021Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Marfan syndrome (MFS) is associated with mutations in fibrillin-1 that predispose afflicted individuals to progressive thoracic aortic aneurysm (TAA) leading to dissection and rupture of the vessel wall. Here we combined computational and experimental approaches to identify and test FDA-approved drugs that may slow or even halt aneurysm progression. Computational analyses of transcriptomic data derived from the aortas of MFS patients and MFS mice (Fbn1mgR/mgR mice) predicted that subcellular pathways associated with reduced muscle contractility are key TAA determinants that could be targeted with the GABAB receptor agonist baclofen. Systemic administration of baclofen to Fbn1mgR/mgR mice validated our computational prediction by mitigating arterial disease progression at the cellular and physiological levels. Interestingly, baclofen improved muscle contraction-related subcellular pathways by upregulating a different set of genes than those downregulated in the aorta of vehicle-treated Fbn1mgR/mgR mice. Distinct transcriptomic profiles were also associated with drug-treated MFS and wild-type mice. Thus, systems pharmacology approaches that compare patient- and mouse-derived transcriptomic data for subcellular pathway-based drug repurposing represent an effective strategy to identify potential new treatments of human diseases.
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