ArticleThe Journal of clinical investigation2020
Targetable cellular signaling events mediate vascular pathology in vascular Ehlers-Danlos syndrome.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05463679 (A Multicenter, Randomized, Double-blind, Placebo-controlled Study of Enzastaurin for the Prevention of Arterial Events in Patients With Vascular Ehlers-Danlos Syndrome), which is not on this map. Cited by 50 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter, Randomized, Double-blind, Placebo-controlled Study of Enzastaurin for the Prevention of Arterial Events in Patients With Vascular Ehlers-Danlos Syndrome (vEDS) Confirmed With COL3A1 Mutations, Followed by an Open Label Extension (OLE)
Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Progress in aorta and peripheral cardiovascular disease research.Cardiovascular research · 2021Pooled it
- The aorta in Marfan syndrome: from molecular mechanisms to mechanobiological dysfunction.Cardiovascular research · 2026Review
- Steroid hormone antagonism affords vascular protection in a mouse model of vascular Ehlers-Danlos syndrome.JCI insight · 2026Article
- Inherited aortopathies and risk of aortic dissection and aortic syndrome in pregnancy.Obstetric medicine · 2026Review
- Cell-dependent contributions of thrombospondin-1 to the rupture of abdominal aortic aneurysm in mice.Cardiovascular research · 2026Article
- Pregnancy and Delivery Outcomes in Vascular Ehlers-Danlos Syndrome: A Retrospective Multicentre Cohort Study.BJOG : an international journal of obstetrics and gynaecology · 2026Article
- Cardiovascular complications of pregnancy.The Journal of clinical investigation · 2026Review
- Novel Aortic Dissection Model Links Endothelial Dysfunction and Immune Infiltration.Circulation research · 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
- The chemical chaperone 4-phenylbutyric acid rescues molecular cell defects of COL3A1 mutations that cause vascular Ehlers Danlos Syndrome.Cell death discovery · 2025Article
- Shaping the future of care for patients with Ehlers-Danlos syndromes: from multidisciplinary management to precision medicine.Orphanet journal of rare diseases · 2025Article
- Mitochondrial NADNature cardiovascular research · 2025Article
- Vascular Ehlers-Danlos syndrome in children: evaluating the importance of diagnosis and follow-up during childhood.European journal of human genetics : EJHG · 2025Article
- Novel Insights into the Aortic Mechanical Properties of Mice Modeling Hereditary Aortic Diseases.Thrombosis and haemostasis · 2025Article
- Pregnancy-related chronic type A aortic dissection highlights the importance of thorough prenatal maternal examination.Journal of cardiothoracic surgery · 2025Article
- Map2k6 is a potent genetic modifier of arterial rupture in vascular Ehlers-Danlos syndrome mice.JCI insight · 2025Article
- Diagnosis of vascular Ehlers Danlos syndrome and management of vascular complications: a vascular surgeons perspective.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2024Article
- Integrative Multi-Omics Approach in Vascular Ehlers-Danlos Syndrome: Further Insights into the Disease Mechanisms by Proteomic Analysis of Patient Dermal Fibroblasts.Biomedicines · 2024Article
- Current Evidence and Future Perspectives in the Medical Management of Vascular Ehlers-Danlos Syndrome: Focus on Vascular Prevention.Journal of clinical medicine · 2024Review
- Coding and Non-Coding Transcriptomic Landscape of Aortic Complications in Marfan Syndrome.International journal of molecular sciences · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal-dominant connective tissue disorder caused by heterozygous mutations in the COL3A1 gene, which encodes the pro-α 1 chain of collagen III. Loss of structural integrity of the extracellular matrix is believed to drive the signs and symptoms of this condition, including spontaneous arterial dissection and/or rupture, the major cause of mortality. We created 2 mouse models of vEDS that carry heterozygous mutations in Col3a1 that encode glycine substitutions analogous to those found in patients, and we showed that signaling abnormalities in the PLC/IP3/PKC/ERK pathway (phospholipase C/inositol 1,4,5-triphosphate/protein kinase C/extracellular signal-regulated kinase) are major mediators of vascular pathology. Treatment with pharmacologic inhibitors of ERK1/2 or PKCβ prevented death due to spontaneous aortic rupture. Additionally, we found that pregnancy- and puberty-associated accentuation of vascular risk, also seen in vEDS patients, was rescued by attenuation of oxytocin and androgen signaling, respectively. Taken together, our results provide evidence that targetable signaling abnormalities contribute to the pathogenesis of vEDS, highlighting unanticipated therapeutic opportunities.
Indexed as
Identifiers
What OpenQuestion holds
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.