ArticleDisease models & mechanisms2013
Functional modeling in zebrafish demonstrates that the atrial-fibrillation-associated gene GREM2 regulates cardiac laterality, cardiomyocyte differentiation and atrial rhythm.
Article in Disease models & mechanisms, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- Transcriptome sequencing-based study on the mechanism of action of Jintiange capsules in regulating synovial mesenchymal stem cells exosomal miRNA and articular chondrocytes mRNA for the treatment of osteoarthritis.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Genetics and Pharmacogenetics of Atrial Fibrillation: A Mechanistic Perspective.JACC. Basic to translational science · 2024Review
- GREM2 inactivation increases trabecular bone mass in mice.Scientific reports · 2024Article
- Zebrafish as a Model for Cardiovascular and Metabolic Disease: The Future of Precision Medicine.Biomedicines · 2024Review
- Genetic and Molecular Underpinnings of Atrial Fibrillation.NPJ cardiovascular health · 2024Article
- Generation of cardiomyocytes from human-induced pluripotent stem cells resembling atrial cells with ability to respond to adrenoceptor agonists.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Zebrafish as a Model of Cardiac Pathology and Toxicity: Spotlight on Uremic Toxins.International journal of molecular sciences · 2023Review
- Genetic and non-genetic risk factors associated with atrial fibrillation.Life sciences · 2022Review
- Deletion of Gremlin-2 alters estrous cyclicity and disrupts female fertility in mice†.Biology of reproduction · 2021Article
- Atrial fibrillation-a complex polygenetic disease.European journal of human genetics : EJHG · 2021Review
- LncRNA DNM3OS regulates GREM2 via miR-127-5p to suppress early chondrogenic differentiation of rat mesenchymal stem cells under hypoxic conditions.Cellular & molecular biology letters · 2021Article
- Genetics and Epigenetics of Atrial Fibrillation.International journal of molecular sciences · 2020Review
- The Genetic Puzzle of Familial Atrial Fibrillation.Frontiers in cardiovascular medicine · 2020Review
- Increase of gremlin 2 with age in human adipose-derived stromal/stem cells and its inhibitory effect on adipogenesis.Regenerative therapy · 2019Article
- Disease Models & Mechanisms in the Age of Big Data.Disease models & mechanisms · 2019Article
- Transcriptome signatures associated with meningioma progression.Acta neuropathologica communications · 2019Article
- Bone morphogenetic protein signaling in inflammation.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Genetics of Atrial Fibrillation.Journal of the American Heart Association · 2018Review
- Coordinated Proliferation and Differentiation of Human-Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Depend on Bone Morphogenetic Protein Signaling Regulation by GREMLIN 2.Stem cells and development · 2017Article
- Structure of Gremlin-2 in Complex with GDF5 Gives Insight into DAN-Family-Mediated BMP Antagonism.Cell reports · 2016Article
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 1 institution in 1 country.
Funding
Abstract
Atrial fibrillation (AF) is the most common cardiac arrhythmia and carries a significant risk of stroke and heart failure. The molecular etiologies of AF are poorly understood, leaving patients with limited therapeutic options. AF has been recognized as an inherited disease in almost 30% of patient cases. However, few genetic loci have been identified and the mechanisms linking genetic variants to AF susceptibility remain unclear. By sequencing 193 probands with lone AF, we identified a Q76E variant within the coding sequence of the bone morphogenetic protein (BMP) antagonist gremlin-2 (GREM2) that increases its inhibitory activity. Functional modeling in zebrafish revealed that, through regulation of BMP signaling, GREM2 is required for cardiac laterality and atrial differentiation during embryonic development. GREM2 overactivity results in slower cardiac contraction rates in zebrafish, and induction of previously identified AF candidate genes encoding connexin-40, sarcolipin and atrial natriuretic peptide in differentiated mouse embryonic stem cells. By live heart imaging in zebrafish overexpressing wild-type or variant GREM2, we found abnormal contraction velocity specifically in atrial cardiomyocytes. These results implicate, for the first time, regulators of BMP signaling in human AF, providing mechanistic insights into the pathogenesis of the disease and identifying potential new therapeutic targets.
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.