ArticleArteriosclerosis, thrombosis, and vascular biology2015
Dimorphic effects of transforming growth factor-β signaling during aortic aneurysm progression in mice suggest a combinatorial therapy for Marfan syndrome.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 1 of them a synthesis that pooled it.
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Who cites it
158 citing papers in PubMed, 1 synthesis or guideline pooled it, 217 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
- Metabolic control of smooth muscle cell phenotype switching in atherosclerosis.Science advances · 2026Article
- The aorta in Marfan syndrome: from molecular mechanisms to mechanobiological dysfunction.Cardiovascular research · 2026Review
- Heritable Thoracic Aortic Diseases in Pediatric Practice: From Molecular Mechanisms to Genotype-Informed Management, a Comprehensive Narrative Review.Journal of clinical medicine · 2026Review
- Mechanotransduction in Marfan Syndrome and Related Aortic Disorders: Insights from Transcriptomic Analyses.Genes · 2026Review
- Aortic asprosin overexpression does not ameliorate disease pathophysiology in a murine model of Marfan syndrome.Scientific reports · 2026Article
- Structural and Signaling Mechanisms of Aortic Wall Failure in Heritable Thoracic Aortic Disease.Cells · 2026Review
- SPP1BMC medicine · 2026Article
- Ischemic stroke as an initial manifestation of Loeys-Dietz syndrome type 3 caused by the recurrent p.Arg287Trp variant inFrontiers in genetics · 2026Article
- Different physiologic biomechanical metrics correlate with aortic diameter increases in normal maturation compared to aneurysm progression in mice.Journal of the mechanical behavior of biomedical materials · 2025Article
- Exploring thoracic aorta ECM alterations in Marfan syndrome: insights into aorta wall structure.Scientific reports · 2025Article
- Integrin-mediated mTOR signaling drives TGF-β overactivity and myxomatous mitral valve degeneration in hypomorphic fibrillin-1 mice.The Journal of clinical investigation · 2025Article
- Semaphorin 3A protects against thoracic aortic aneurysm dissection by suppressing aortic angiogenesis.Angiogenesis · 2025Article
- Sex- and age-dependent neurovascular abnormalities linked to neuroinflammation lead to exacerbated post-ischemic brain injury in Marfan syndrome mice.Redox biology · 2025Article
- Recommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- 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
- Novel Insights into the Aortic Mechanical Properties of Mice Modeling Hereditary Aortic Diseases.Thrombosis and haemostasis · 2025Article
- 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
- Elevated Dickkopf 3 Promotes Abdominal Aortic Aneurysm Formation via Modulated Phenotype Switch of Vascular Smooth Muscle Cells.Research (Washington, D.C.) · 2025Article
- Complement C3a/C3aR inhibition alleviates the formation of aortic aneurysm in Marfan syndrome mice.BMC cardiovascular disorders · 2024Article
98 more citing papers are in PubMed but not listed here.
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10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveStudies of mice with mild Marfan syndrome (MFS) have correlated the development of thoracic aortic aneurysm (TAA) with improper stimulation of noncanonical (Erk-mediated) TGFβ signaling by the angiotensin type I receptor (AT1r). This correlation was largely based on comparable TAA modifications by either systemic TGFβ neutralization or AT1r antagonism. However, subsequent investigations have called into question some key aspects of this mechanism of arterial disease in MFS. To resolve these controversial points, here we made a head-to-head comparison of the therapeutic benefits of TGFβ neutralization and AT1r antagonism in mice with progressively severe MFS (Fbn1(mgR/mgR) mice). APPROACH AND
resultsAneurysm growth, media degeneration, aortic levels of phosphorylated Erk and Smad proteins and the average survival of Fbn1(mgR/mgR) mice were compared after a ≈3-month-long treatment with placebo and either the AT1r antagonist losartan or the TGFβ-neutralizing antibody 1D11. In contrast to the beneficial effect of losartan, TGFβ neutralization either exacerbated or mitigated TAA formation depending on whether treatment was initiated before (postnatal day 16; P16) or after (P45) aneurysm formation, respectively. Biochemical evidence-related aneurysm growth with Erk-mediated AT1r signaling, and medial degeneration with TGFβ hyperactivity that was in part AT1r dependent. Importantly, P16-initiated treatment with losartan combined with P45-initiated administration of 1D11 prevented death of Fbn1(mgR/mgR) mice from ruptured TAA.
conclusionsBy demonstrating that promiscuous AT1r and TGFβ drive partially overlapping processes of arterial disease in MFS mice, our study argues for a therapeutic strategy against TAA that targets both signaling pathways although sparing the early protective role of TGFβ.
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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.