ArticleThe Journal of clinical investigation2014
Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome.
Article in The Journal of clinical investigation, 2014. 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 83 papers, 2 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
83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 142 citations in OpenAlex.
- Skeletal muscle alterations in Marfan syndrome: a systematic review.Journal of muscle research and cell motility · 2025Pooled it
- A Role for Photobiomodulation in the Prevention of Myocardial Ischemic Reperfusion Injury: A Systematic Review and Potential Molecular Mechanisms.Scientific reports · 2017Pooled it
- 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
- Alterations in ascending aortic hemodynamics and aortic length correlate with sex-specific thoracic aortic aneurysm dilation and lifespan in a mouse model of severe Marfan syndrome.Computers in biology and medicine · 2026Article
- Collagen XV preserves heart function and protects from pathological remodelling after myocardial infarction.The FEBS journal · 2026Article
- Is cardiomyopathy intrinsic to Marfan syndrome?Pediatric research · 2025Article
- Intrinsic cardiomyopathy in pediatric Marfan syndrome: predictive factors and risk assessments.Pediatric research · 2025Article
- Automated atomic force microscopy analysis using convolutional and recurrent neural networks.Biophysical journal · 2025Article
- Endothelial Cell Senescence in Marfan Syndrome: Pathogenesis and Therapeutic Potential of TGF-β Pathway Inhibition.Journal of the American Heart Association · 2025Article
- Marfan syndrome cardiomyocytes show excess of titin isoform N2BA and extended sarcomeric M-band.The Journal of general physiology · 2025Article
- Induction of cardiac fibulin-4 protects against pressure overload-induced cardiac hypertrophy and heart failure.Communications biology · 2025Article
- Hemodynamic disturbance and mTORC1 activation: Unveiling the biomechanical pathogenesis of thoracic aortic aneurysms in Marfan syndrome.Journal of pharmaceutical analysis · 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
- Angiotensinogen as a Therapeutic Target for Cardiovascular and Metabolic Diseases.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- In vivo phenotypic vascular dysfunction extends beyond the aorta in a mouse model for fibrillin-1 (Fbn1) mutation.Scientific reports · 2024Article
- Insights Into the Role of Angiotensin-II ATHypertension (Dallas, Tex. : 1979) · 2024Review
- Environmental stiffness restores mechanical homeostasis in vimentin-depleted cells.Scientific reports · 2023Article
- Abnormal Left Ventricular Strain Correlates with Left Ventricular Dysfunction but not Aortic Pathology in Marfan Syndrome in Children.Pediatric cardiology · 2023Article
- Nuclear mechanosignaling in striated muscle diseases.Frontiers in physiology · 2023Review
23 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
12 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with Marfan syndrome (MFS), a multisystem disorder caused by mutations in the gene encoding the extracellular matrix (ECM) protein fibrillin 1, are unusually vulnerable to stress-induced cardiac dysfunction. The prevailing view is that MFS-associated cardiac dysfunction is the result of aortic and/or valvular disease. Here, we determined that dilated cardiomyopathy (DCM) in fibrillin 1-deficient mice is a primary manifestation resulting from ECM-induced abnormal mechanosignaling by cardiomyocytes. MFS mice displayed spontaneous emergence of an enlarged and dysfunctional heart, altered physical properties of myocardial tissue, and biochemical evidence of chronic mechanical stress, including increased angiotensin II type I receptor (AT1R) signaling and abated focal adhesion kinase (FAK) activity. Partial fibrillin 1 gene inactivation in cardiomyocytes was sufficient to precipitate DCM in otherwise phenotypically normal mice. Consistent with abnormal mechanosignaling, normal cardiac size and function were restored in MFS mice treated with an AT1R antagonist and in MFS mice lacking AT1R or β-arrestin 2, but not in MFS mice treated with an angiotensin-converting enzyme inhibitor or lacking angiotensinogen. Conversely, DCM associated with abnormal AT1R and FAK signaling was the sole abnormality in mice that were haploinsufficient for both fibrillin 1 and β1 integrin. Collectively, these findings implicate fibrillin 1 in the physiological adaptation of cardiac muscle to elevated workload.
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.