ArticleCirculation research2014
Overexpression of the Na+/K+ ATPase α2 but not α1 isoform attenuates pathological cardiac hypertrophy and remodeling.
Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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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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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.
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Who cites it
41 citing papers in PubMed, 67 citations in OpenAlex.
- Role of NaInternational journal of molecular sciences · 2024Review
- Sensational site: the sodium pump ouabain-binding site and its ligands.American journal of physiology. Cell physiology · 2024Review
- The GENTIL Method for Isolation of Human Adult Cardiomyocytes from Cryopreserved Tissue for Proteomic Analyses.Methods in molecular biology (Clifton, N.J.) · 2024Article
- The Na/K-ATPase α1/Src Signaling Axis Regulates Mitochondrial Metabolic Function and Redox Signaling in Human iPSC-Derived Cardiomyocytes.Biomedicines · 2023Article
- Hypoxic Stress-Dependent Regulation of Na,K-ATPase in Ischemic Heart Disease.International journal of molecular sciences · 2023Review
- Article
- Augmented Ouabain-Induced Vascular Response Reduces Cardiac Efficiency in Mice with Migraine-Associated Mutation in the NaBiomedicines · 2023Article
- The NaFrontiers in endocrinology · 2023Review
- Fluorescence lifetime imaging microscopy reveals sodium pump dimers in live cells.The Journal of biological chemistry · 2022Article
- Migraine-Associated Mutation in the Na,K-ATPase Leads to Disturbances in Cardiac Metabolism and Reduced Cardiac Function.Journal of the American Heart Association · 2022Article
- Protective Effect of Trimetazidine on Potassium Ion Homeostasis in Myocardial Tissue in Mice with Heart Failure.BioMed research international · 2022Article
- Regulation of Cardiac Contractility by the Alpha 2 Subunit of the NaFrontiers in physiology · 2022Review
- Cardiomyocyte NaAmerican journal of physiology. Heart and circulatory physiology · 2021Article
- Calcium Signaling Silencing in Atrial Fibrillation: Implications for Atrial Sodium Homeostasis.International journal of molecular sciences · 2021Review
- The heart in hypertension.Journal of human hypertension · 2021Article
- The αScientific reports · 2020Article
- Amyloid Beta Oligomers Target to Extracellular and Intracellular Neuronal Synaptic Proteins in Alzheimer's Disease.Frontiers in neurology · 2019Article
- Stimulation of NaOxidative medicine and cellular longevity · 2019Article
- Role of the βMolecular and cellular biochemistry · 2018Article
- Klotho attenuates isoproterenol-induced hypertrophic response in H9C2 cells by activating NaIn vitro cellular & developmental biology. Animal · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
rationaleThe Na+ / K+ ATPase (NKA) directly regulates intracellular Na+ levels, which in turn indirectly regulates Ca2+ levels by proximally controlling flux through the Na+ / Ca2+ exchanger (NCX1). Elevated Na+ levels have been reported during heart failure, which permits some degree of reverse-mode Ca2+ entry through NCX1, as well as less efficient Ca2+ clearance.
objectiveTo determine whether maintaining lower intracellular Na+ levels by NKA overexpression in the heart would enhance forward-mode Ca2+ clearance and prevent reverse-mode Ca2+ entry through NCX1 to protect the heart. METHODS AND
resultsCardiac-specific transgenic mice overexpressing either NKA-α1 or NKA-α2 were generated and subjected to pressure overload hypertrophic stimulation. We found that although increased expression of NKA-α1 had no protective effect, overexpression of NKA-α2 significantly decreased cardiac hypertrophy after pressure overload in mice at 2, 10, and 16 weeks of stimulation. Remarkably, total NKA protein expression and activity were not altered in either of these 2 transgenic models because increased expression of one isoform led to a concomitant decrease in the other endogenous isoform. NKA-α2 overexpression but not NKA-α1 led to significantly faster removal of bulk Ca2+ from the cytosol in a manner requiring NCX1 activity. Mechanistically, overexpressed NKA-α2 showed greater affinity for Na+ compared with NKA-α1, leading to more efficient clearance of this ion. Furthermore, overexpression of NKA-α2 but not NKA-α1 was coupled to a decrease in phospholemman expression and phosphorylation, which would favor greater NKA activity, NCX1 activity, and Ca2+ removal.
conclusionsOur results suggest that the protective effect produced by increased expression of NKA-α2 on the heart after pressure overload is due to more efficient Ca2+ clearance because this isoform of NKA preferentially enhances NCX1 activity compared with NKA-α1.
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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.