ArticleJCI insight2017
Nonmyocyte ERK1/2 signaling contributes to load-induced cardiomyopathy in Marfan mice.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Integrated microarray-based and single-cell transcriptomic analyses reveal cell adhesion-related fibrotic remodeling signatures in heart failure.Frontiers in molecular biosciences · 2026Article
- Intrinsic cardiomyopathy in pediatric Marfan syndrome: predictive factors and risk assessments.Pediatric research · 2025Article
- The Extracellular Matrix and Cardiac Pressure Overload: Focus on Novel Treatment Targets.Cells · 2024Review
- Coding and Non-Coding Transcriptomic Landscape of Aortic Complications in Marfan Syndrome.International journal of molecular sciences · 2024Review
- Prostaglandin ICellular and molecular life sciences : CMLS · 2024Article
- Marfan syndrome: insights from animal models.Frontiers in genetics · 2024Review
- Article
- European Society of Toxicologic Pathology (Pathology 2.0 Molecular Pathology Special Interest Group): Review of In Situ Hybridization Techniques for Drug Research and Development.Toxicologic pathology · 2023Review
- Latent TGFβ-binding proteins 1 and 3 protect the larval zebrafish outflow tract from aneurysmal dilatation.Disease models & mechanisms · 2022Article
- Exploring the cardiac ECM during fibrosis: A new era with next-gen proteomics.Frontiers in molecular biosciences · 2022Review
- Comprehensive Characterization of Arterial and Cardiac Function in Marfan Syndrome-Can Biomarkers Help Improve Outcome?Frontiers in physiology · 2022Article
- Marfan syndrome.Nature reviews. Disease primers · 2021Review
- Postsystolic thickening is a potential new clinical sign of injured myocardium in marfan syndrome.Scientific reports · 2021Article
- Non-aortic cardiovascular disease in Marfan syndrome: a nationwide epidemiological study.Clinical research in cardiology : official journal of the German Cardiac Society · 2021Article
- Cardiomyopathy in Genetic Aortic Diseases.Frontiers in pediatrics · 2021Review
- Myocardial disease and ventricular arrhythmia in Marfan syndrome: a prospective study.Orphanet journal of rare diseases · 2020Article
- Effects of fibrillin mutations on the behavior of heart muscle cells in Marfan syndrome.Scientific reports · 2020Article
- Myocardial Function, Heart Failure and Arrhythmia in Marfan Syndrome: A Systematic Literature Review.Diagnostics (Basel, Switzerland) · 2020Review
- Spontaneous Right Ventricular Pseudoaneurysms and Increased Arrhythmogenicity in a Mouse Model of Marfan Syndrome.International journal of molecular sciences · 2020Article
- Localized Antileptin Therapy Prevents Aortic Root Dilatation and Preserves Left Ventricular Systolic Function in a Murine Model of Marfan Syndrome.Journal of the American Heart Association · 2020Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
Abstract
Among children with the most severe presentation of Marfan syndrome (MFS), an inherited disorder of connective tissue caused by a deficiency of extracellular fibrillin-1, heart failure is the leading cause of death. Here, we show that, while MFS mice (Fbn1C1039G/+ mice) typically have normal cardiac function, pressure overload (PO) induces an acute and severe dilated cardiomyopathy in association with fibrosis and myocyte enlargement. Failing MFS hearts show high expression of TGF-β ligands, with increased TGF-β signaling in both nonmyocytes and myocytes; pathologic ERK activation is restricted to the nonmyocyte compartment. Informatively, TGF-β, angiotensin II type 1 receptor (AT1R), or ERK antagonism (with neutralizing antibody, losartan, or MEK inhibitor, respectively) prevents load-induced cardiac decompensation in MFS mice, despite persistent PO. In situ analyses revealed an unanticipated axis of activation in nonmyocytes, with AT1R-dependent ERK activation driving TGF-β ligand expression that culminates in both autocrine and paracrine overdrive of TGF-β signaling. The full compensation seen in wild-type mice exposed to mild PO correlates with enhanced deposition of extracellular fibrillin-1. Taken together, these data suggest that fibrillin-1 contributes to cardiac reserve in the face of hemodynamic stress, critically implicate nonmyocytes in disease pathogenesis, and validate ERK as a therapeutic target in MFS-related cardiac decompensation.
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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.