ArticleJournal of the American Heart Association2015
LKB1 knockout mouse develops spontaneous atrial fibrillation and provides mechanistic insights into human disease process.
Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 106 citations in OpenAlex.
- Increased Right Atrial FDG Uptake in Persistent Atrial Fibrillation: Insights Across Young vs. Old Age Groups.Korean circulation journal · 2026Article
- Sex-specific impact of body mass index on recurrence of atrial fibrillation after catheter ablation.Heart rhythm O2 · 2026Article
- Metabolic and Inflammatory Mechanisms Driving Atrial Fibrillation.Annual review of pharmacology and toxicology · 2026Review
- Metabolic Remodeling and Mitochondrial Stress in Atrial Fibrillation: Mechanisms and Translational Targets.Reviews in cardiovascular medicine · 2025Review
- Generation and characterization of a DYNLT1-knockout mouse model reveals electrophysiological alterations and potential mechanistic contributors to atrial fibrillation.Biology open · 2025Article
- A Novel Protein NAB1-356 Encoded by circRNA circNAB1 Mitigates Atrial Fibrillation by Reducing Inflammation and Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Investigating Left Atrial Diameter and Heart Failure Onset in Middle-Aged and Elderly: A Retrospective-Prospective Study.Clinical cardiology · 2025Article
- Relaxin-2 Exhibits a Beneficial Role in Energy Metabolism to Alleviate Atrial Fibrillation Susceptibility.ACS pharmacology & translational science · 2025Article
- The gut microbial metabolite phenylacetylglutamine increases susceptibility to atrial fibrillation after myocardial infarction through ferroptosis and NLRP3 inflammasome.Apoptosis : an international journal on programmed cell death · 2025Article
- Advancing Atrial Fibrillation Research: The Role of Animal Models, Emerging Technologies and Translational Challenges.Biomedicines · 2025Review
- Animal and cellular models of atrial fibrillation: a review.Frontiers in cardiovascular medicine · 2025Review
- ANXA1-FPR2 axis mitigates the susceptibility to atrial fibrillation in obesity via rescuing AMPK activity in response to lipid overload.Cardiovascular diabetology · 2024Article
- Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation.iScience · 2024Article
- Exercise-Dependent Modulation of Immunological Response Pathways in Endurance Athletes With and Without Atrial Fibrillation.Journal of the American Heart Association · 2024Article
- Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights.Vascular health and risk management · 2024Review
- Genetic and Molecular Underpinnings of Atrial Fibrillation.NPJ cardiovascular health · 2024Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- Towards Improved HumanBiomedicines · 2023Review
- Mouse models of spontaneous atrial fibrillation.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- PI3K(p110α) as a determinant and gene therapy for atrial enlargement in atrial fibrillation.Molecular and cellular biochemistry · 2023Review
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4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAtrial fibrillation (AF) is a complex disease process, and the molecular mechanisms underlying initiation and progression of the disease are unclear. Consequently, AF has been difficult to model. In this study, we have presented a novel transgenic mouse model of AF that mimics human disease and characterized the mechanisms of atrial electroanatomical remodeling in the genesis of AF. METHODS AND
resultsCardiac-specific liver kinase B1 (LKB1) knockout (KO) mice were generated, and 47% aged 4 weeks and 95% aged 12 weeks developed spontaneous AF from sinus rhythm by demonstrating paroxysmal and persistent stages of the disease. Electrocardiographic characteristics of sinus rhythm were similar in KO and wild-type mice. Atrioventricular block and atrial flutter were common in KO mice. Heart rate was slower with persistent AF. In parallel with AF, KO mice developed progressive biatrial enlargement with inflammation, heterogeneous fibrosis, and loss of cardiomyocyte population with apoptosis and necrosis. Atrial tissue was infiltrated with inflammatory cells. C-reactive protein, interleukin 6, and tumor necrosis factor α were significantly elevated in serum. KO atria demonstrated elevated reactive oxygen species and decreased AMP-activated protein kinase activity. Cardiomyocyte and myofibrillar ultrastructure were disrupted. Intercellular matrix and gap junction were interrupted. Connexins 40 and 43 were reduced. Persistent AF caused left ventricular dysfunction and heart failure. Survival and exercise capacity were worse in KO mice.
conclusionsLKB1 KO mice develop spontaneous AF from sinus rhythm and progress into persistent AF by replicating the human AF disease process. Progressive inflammatory atrial cardiomyopathy is the genesis of AF, through mechanistic electrical and structural remodeling.
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