ArticleJournal of the American College of Cardiology2015
Contractile Function During Angiotensin-II Activation: Increased Nox2 Activity Modulates Cardiac Calcium Handling via Phospholamban Phosphorylation.
Article in Journal of the American College of Cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 93 citations in OpenAlex.
- Acute intermittent hypercapnic hypoxia augments left ventricular contractility.The Journal of physiology · 2026Article
- Temporal changes in first-phase ejection fraction during evolution of heart failure with preserved ejection fraction and afterload-induced heart failure in mice.Journal of physiology and biochemistry · 2026Article
- Mechanism of RNA Oxidation and Its Inhibitor Involved in Ang II-Induced Cardiomyocyte Hypertrophy.Aging medicine (Milton (N.S.W)) · 2025Article
- Cardiomyocyte Rac1 signaling in hypertrophy, arrhythmia, and cardiac stress adaptation.Journal of molecular and cellular cardiology plus · 2025Review
- Mechanisms underlying atrial fibrillation in chronic kidney disease.Journal of molecular and cellular cardiology · 2025Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Review
- SERCA2a dysfunction in the pathophysiology of heart failure with preserved ejection fraction: a direct role is yet to be established.Heart failure reviews · 2025Review
- NADPH Oxidases in Cancer Therapy-Induced Cardiotoxicity: Mechanisms and Therapeutic Approaches.Cardiovascular toxicology · 2025Review
- Remodeling of the cardiac striatin interactome and its dynamics in the diabetic heart.Scientific reports · 2025Article
- PKM2 regulates metabolic flux and oxidative stress in the murine heart.Physiological reports · 2024Article
- Mechanisms of stretch-induced electro-anatomical remodeling and atrial arrhythmogenesis.Journal of molecular and cellular cardiology · 2024Review
- Vitamin C as Scavenger of Reactive Oxygen Species during Healing after Myocardial Infarction.International journal of molecular sciences · 2024Review
- Nongenetic Optical Modulation of Pluripotent Stem Cells Derived Cardiomyocytes Function in the Red Spectral Range.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Inhibition of lncRNA DANCR Prevents Heart Failure by Ameliorating Cardiac Hypertrophy and Fibrosis Via Regulation of the miR-758-3p/PRG4/Smad Axis.Journal of cardiovascular translational research · 2023Article
- Detergent-Based Decellularization for Anisotropic Cardiac-Specific Extracellular Matrix Scaffold Generation.Biomimetics (Basel, Switzerland) · 2023Article
- Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection.Redox biology · 2023Review
- Acute phosphatidylinositol 4,5 bisphosphate depletion destabilizes sarcolemmal expression of cardiac L-type CaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Endothelial cell-specific roles for tetrahydrobiopterin in myocardial function, cardiac hypertrophy, and response to myocardial ischemia-reperfusion injury.American journal of physiology. Heart and circulatory physiology · 2023Article
- Calcium and Reactive Oxygen Species Signaling Interplays in Cardiac Physiology and Pathologies.Antioxidants (Basel, Switzerland) · 2023Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundRenin-angiotensin system activation is a feature of many cardiovascular conditions. Activity of myocardial reduced nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2 or Nox2) is enhanced by angiotensin II (Ang II) and contributes to increased hypertrophy, fibrosis, and adverse remodeling. Recent studies found that Nox2-mediated reactive oxygen species production modulates physiological cardiomyocyte function.
objectivesThis study sought to investigate the effects of cardiomyocyte Nox2 on contractile function during increased Ang II activation.
methodsWe generated a cardiomyocyte-targeted Nox2-transgenic mouse model and studied the effects of in vivo and ex vivo Ang II stimulation, as well as chronic aortic banding.
resultsChronic subpressor Ang II infusion induced greater cardiac hypertrophy in transgenic than wild-type mice but unexpectedly enhanced contractile function. Acute Ang II treatment also enhanced contractile function in transgenic hearts in vivo and transgenic cardiomyocytes ex vivo. Ang II-stimulated Nox2 activity increased sarcoplasmic reticulum (SR) Ca(2+) uptake in transgenic mice, increased the Ca(2+) transient and contractile amplitude, and accelerated cardiomyocyte contraction and relaxation. Elevated Nox2 activity increased phospholamban phosphorylation in both hearts and cardiomyocytes, related to inhibition of protein phosphatase 1 activity. In a model of aortic banding-induced chronic pressure overload, heart function was similarly depressed in transgenic and wild-type mice.
conclusionsWe identified a novel mechanism in which Nox2 modulates cardiomyocyte SR Ca(2+) uptake and contractile function through redox-regulated changes in phospholamban phosphorylation. This mechanism can drive increased contractility in the short term in disease states characterized by enhanced renin-angiotensin system activation.
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