Observational studyeLife2015
A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome.
Observational study in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01322165 (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions), which is not on this map. Cited by 64 papers, 4 of them syntheses 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.
National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
Who cites it
64 citing papers in PubMed, 4 syntheses or guidelines pooled it, 113 citations in OpenAlex.
- Aortic Remodeling in Patients with Arterial Hypertension: Pathophysiological Mechanisms, Therapeutic Interventions and Preventive Strategies-A Position Paper from the Heart and Hypertension Working Group of the Italian Society of Hypertension.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2025Guideline
- 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.The Journal of thoracic and cardiovascular surgery · 2023Guideline
- Guideline
- 2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.Journal of the American College of Cardiology · 2022Guideline
- Cautionary Data on Antihypertensives in Aortic Diseases.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Introducing Allopurinol to the Medical Treatment of Marfan Syndrome: Advantages, Limitations, and Potential Extension to other Aortopathies.Cardiovascular drugs and therapy · 2026Review
- The aorta in Marfan syndrome: from molecular mechanisms to mechanobiological dysfunction.Cardiovascular research · 2026Review
- Hypertension drives thoracic aortic aneurysm and dissection in male, but not female, Marfan mice.Journal of the mechanical behavior of biomedical materials · 2026Article
- Mechanotransduction in Marfan Syndrome and Related Aortic Disorders: Insights from Transcriptomic Analyses.Genes · 2026Review
- Preclinical modeling of Loeys-Dietz syndrome: insights into mechanisms and therapy.Orphanet journal of rare diseases · 2026Review
- Loss of CASQ2 promotes vascular smooth muscle cell phenotypic switching in aortic dissection uncovered by integrated single-cell transcriptomics.BMC medical genomics · 2026Article
- Inherited aortopathies and risk of aortic dissection and aortic syndrome in pregnancy.Obstetric medicine · 2026Review
- Calcium channel blockers increase the risk of aortic aneurysm and dissection.Nature communications · 2025Article
- Management and outcomes of thoracic dissection in older adults.Seminars in vascular surgery · 2025Review
- Deficiency of fibroblast growth factor 2 promotes contractile phenotype of pericytes in ascending thoracic aortic aneurysm.American journal of physiology. Heart and circulatory physiology · 2025Article
- Mitochondrial NADNature cardiovascular research · 2025Article
- The TRPM7 chanzyme in smooth muscle cells drives abdominal aortic aneurysm in mice.Nature cardiovascular research · 2025Article
- Therapeutic Opportunities of Marfan Syndrome: Current Perspectives.Drug design, development and therapy · 2025Review
- Missense variants ofMolecular genetics and metabolism reports · 2024Article
- Management of aortic disease in children with FBN1-related Marfan syndrome.European heart journal · 2024Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 8 institutions in 4 countries.
Funding
Abstract
Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents.
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.