ArticlePLoS genetics2018
Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 52 citations in OpenAlex.
- Rethinking Left Ventricular Noncompaction and Excessive Left Ventricular Trabeculation: Development, Genetics, and a Proposed Conceptual Framework.Journal of clinical medicine · 2026Review
- The spongy heart paradox: balancing bleeding and clotting risk in left ventricular noncompaction cardiomyopathy.Heart failure reviews · 2026Review
- Benchmarking and optimizing Perturb-seq in differentiating human pluripotent stem cells.Stem cell reports · 2025Article
- NKX2-5 Mutation and ICD Implantation in a Pregnant AV Block Patient.JACC. Case reports · 2025Article
- Left Ventricular Noncompaction Cardiomyopathy in Children: A Focus on Genetic and Molecular Mechanisms.Reviews in cardiovascular medicine · 2025Review
- Preliminary investigation into the mechanical implications of excessive trabecularization in the left ventricle.Quantitative imaging in medicine and surgery · 2025Article
- Patterning Defects in Mice with Defective Ventricular Wall Maturation and Cardiomyopathy.Journal of cardiovascular development and disease · 2025Article
- Patterns of left ventricular trabeculation in hypertrophic cardiomyopathy.BMC medicine · 2025Article
- Conduction defects and arrhythmias inFrontiers in physiology · 2025Article
- Cardiac electrical abnormalities in a mouse model of left ventricular non-compaction cardiomyopathy.PloS one · 2025Article
- Left Ventricular Non-Compaction: Evolving Concepts.Journal of clinical medicine · 2024Review
- RETRACTED: Left Ventricular Non-Compaction in Children: Aetiology and Diagnostic CriteriaDiagnostics (Basel, Switzerland) · 2024Review
- Molecular Pathways and Animal Models of Ebstein's Anomaly.Advances in experimental medicine and biology · 2024Review
- Missense Mutation in Human CHD4 Causes Ventricular Noncompaction by Repressing ADAMTS1.Circulation research · 2023Article
- Article
- Endothelial deletion of PTBP1 disrupts ventricular chamber development.Nature communications · 2023Article
- Excessive Trabeculation of the Left Ventricle: JACC: Cardiovascular Imaging Expert Panel Paper.JACC. Cardiovascular imaging · 2023Review
- Equal force generation potential of trabecular and compact wall ventricular cardiomyocytes.iScience · 2022Article
- Left ventricular noncompaction: a disorder with genotypic and phenotypic heterogeneity-a narrative review.Cardiovascular diagnosis and therapy · 2022Review
- Activation of Nkx2.5 transcriptional program is required for adult myocardial repair.Nature communications · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Left ventricular non-compaction (LVNC) is a rare cardiomyopathy associated with a hypertrabeculated phenotype and a large spectrum of symptoms. It is still unclear whether LVNC results from a defect of ventricular trabeculae development and the mechanistic basis that underlies the varying severity of this pathology is unknown. To investigate these issues, we inactivated the cardiac transcription factor Nkx2-5 in trabecular myocardium at different stages of trabecular morphogenesis using an inducible Cx40-creERT2 allele. Conditional deletion of Nkx2-5 at embryonic stages, during trabecular formation, provokes a severe hypertrabeculated phenotype associated with subendocardial fibrosis and Purkinje fiber hypoplasia. A milder phenotype was observed after Nkx2-5 deletion at fetal stages, during trabecular compaction. A longitudinal study of cardiac function in adult Nkx2-5 conditional mutant mice demonstrates that excessive trabeculation is associated with complex ventricular conduction defects, progressively leading to strain defects, and, in 50% of mutant mice, to heart failure. Progressive impaired cardiac function correlates with conduction and strain defects independently of the degree of hypertrabeculation. Transcriptomic analysis of molecular pathways reflects myocardial remodeling with a larger number of differentially expressed genes in the severe versus mild phenotype and identifies Six1 as being upregulated in hypertrabeculated hearts. Our results provide insights into the etiology of LVNC and link its pathogenicity with compromised trabecular development including compaction defects and ventricular conduction system hypoplasia.
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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.