ArticleCardiovascular research2015
LKB1 deletion causes early changes in atrial channel expression and electrophysiology prior to atrial fibrillation.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Atrial Cardiomyopathy in Atrial Fibrillation: Mechanistic Pathways and Emerging Treatment Concepts.Journal of clinical medicine · 2025Review
- Investigating Left Atrial Diameter and Heart Failure Onset in Middle-Aged and Elderly: A Retrospective-Prospective Study.Clinical cardiology · 2025Article
- Atrial cardiomyopathy revisited-evolution of a concept: a clinical consensus statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asian Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS).Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Article
- Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights.Vascular health and risk management · 2024Review
- Mouse models of spontaneous atrial fibrillation.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Cannabinoid receptor agonist attenuates angiotensin II-induced enlargement and mitochondrial dysfunction in rat atrial cardiomyocytes.Frontiers in pharmacology · 2023Article
- Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation.JCI insight · 2022Article
- Research Priorities in the Secondary Prevention of Atrial Fibrillation: A National Heart, Lung, and Blood Institute Virtual Workshop Report.Journal of the American Heart Association · 2021Article
- Transcriptional factors in calcium mishandling and atrial fibrillation development.Pflugers Archiv : European journal of physiology · 2021Review
- Activation of AMP-Activated Protein Kinases Prevents Atrial Fibrillation.Journal of cardiovascular translational research · 2021Article
- Association Between Obesity-Mediated Atrial Fibrillation and Therapy With Sodium Channel Blocker Antiarrhythmic Drugs.JAMA cardiology · 2020Observational
- Molecular Mechanism of the Association Between Atrial Fibrillation and Heart Failure Includes Energy Metabolic Dysregulation Due to Mitochondrial Dysfunction.Journal of cardiac failure · 2019Article
- Cardiomyocyte d-dopachrome tautomerase protects against heart failure.JCI insight · 2019Article
- Arrhythmogenic Substrates for Atrial Fibrillation in Obesity.Frontiers in physiology · 2018Review
- Oxidative stress and inflammation as central mediators of atrial fibrillation in obesity and diabetes.Cardiovascular diabetology · 2017Review
- Angiotensin II affects inflammation mechanisms via AMPK-related signalling pathways in HL-1 atrial myocytes.Scientific reports · 2017Article
- Deletion of Lkb1 in adult mice results in body weight reduction and lethality.Scientific reports · 2016Article
- The value of basic research insights into atrial fibrillation mechanisms as a guide to therapeutic innovation: a critical analysis.Cardiovascular research · 2016Review
- Electrophysiological Mechanisms of Bayés Syndrome: Insights from Clinical and Mouse Studies.Frontiers in physiology · 2016Review
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Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
aimsLiver kinase B1 (LKB1) is a protein kinase that activates the metabolic regulator AMP-activated protein kinase (AMPK) and other related kinases. Deletion of LKB1 in mice leads to cardiomyopathy and atrial fibrillation (AF). However, the specific role of the LKB1 pathway in early atrial biology remains unknown. Thus, we investigated whether LKB1 deletion altered atrial channel expression and electrophysiological function in a cardiomyocyte-specific knockout mouse model. METHODS AND
resultsWe performed a systematic comparison of αMHC-Cre LKB1(fl/fl) and littermate LKB1(fl/fl) male mice. This included analysis of gene expression, histology, and echocardiography, as well as cellular and tissue-level electrophysiology using patch-clamp recordings in vitro, optical mapping ex vivo, and ECG recordings in vivo. At postnatal day 1, atrial depolarization was prolonged, and Nav1.5 and Cx40 expression were markedly down-regulated in MHC-Cre LKB1(fl/fl) mice. Inward sodium current density was significantly decreased in MHC-Cre LKB1(fl/fl) neonatal atrial myocytes. Subsequently, additional alterations in atrial channel expression, atrial fibrosis, and spontaneous onset of AF developed by 2 weeks of age. In adult mice, abnormalities of interatrial conduction and bi-atrial electrical coupling were observed, likely promoting the perpetuation of AF. Mice with AMPK-inactivated hearts demonstrated modest overlap in channel expression with MHC-Cre LKB1(fl/fl) hearts, but retained normal structure, electrophysiological function and contractility.
conclusionsDeletion of LKB1 causes early defects in atrial channel expression, action potential generation and conduction, which precede widespread atrial remodelling, fibrosis and AF. LKB1 is critical for normal atrial growth and electrophysiological function.
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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.