ArticleJCI insight2017
Inhibition of NADPH oxidase 2 (NOX2) prevents sepsis-induced cardiomyopathy by improving calcium handling and mitochondrial function.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 155 citations in OpenAlex.
- Impact of Treatment with Antioxidants as an Adjuvant to Standard Therapy in Patients with Septic Shock: Analysis of the Correlation between Cytokine Storm and Oxidative Stress and Therapeutic Effects.International journal of molecular sciences · 2023Trial
- Epigenetic Mechanisms in Sepsis-Induced Cardiomyopathy: From Pathophysiology to Therapeutic Targets.International journal of molecular sciences · 2026Review
- Association between corrected serum calcium levels and 28-day mortality in patients with sepsis: A cohort study.Medicine · 2026Article
- Doxorubicin-Induced Cardiac Remodeling: Mechanisms and Mitigation Strategies.Cardiovascular drugs and therapy · 2026Review
- Sepsis-induced cardiomyopathy: mechanisms, epidemiology, diagnosis, and treatments.Frontiers in immunology · 2026Review
- Phagocyte NADPH Oxidase NOX2-Derived Reactive Oxygen Species in Antimicrobial Defense: Mechanisms, Regulation, and Therapeutic Potential-A Narrative Review.Antioxidants (Basel, Switzerland) · 2025Review
- Nogo-B impairs efferocytosis in monocyte-derived macrophages and exacerbates septic liver injury.JHEP reports : innovation in hepatology · 2025Article
- Article
- Mitochondria at the Heart of Sepsis: Mechanisms, Metabolism, and Sex Differences.International journal of molecular sciences · 2025Review
- Multifaceted roles of neutrophils in cardiac disease.Journal of leukocyte biology · 2025Review
- Roles and Therapeutic Targeting of Exosomes in Sepsis-Induced Cardiomyopathy.Journal of cellular and molecular medicine · 2025Review
- Sepsis-induced cardiac dysfunction: mitochondria and energy metabolism.Intensive care medicine experimental · 2025Review
- Understanding chronic inflammation: couplings between cytokines, ROS, NO, CaFrontiers in immunology · 2025Review
- Polycystic Ovary Syndrome May Be Associated With a Novel Mitochondrial tRNAHuman mutation · 2025Article
- Characteristics and risk factors for mortality in patients with acute coronary syndrome concomitant sepsis: a retrospective multicenter cohort study.Frontiers in cardiovascular medicine · 2025Article
- The Role of Mitochondrial Dysfunction and Inflammatory Response in the Pathogenesis of Sepsis-Induced Myocardial Injury: A Mechanistic Study.Journal of inflammation research · 2025Review
- Article
- An optimized Langendorff-free method for isolation and characterization of primary adult cardiomyocytes.BMC cardiovascular disorders · 2024Article
- An Optimized Langendorff-free Method for Isolation and Characterization of Primary Adult Cardiomyocytes.Research square · 2024Article
- Bisphosphoglycerate mutase predicts myocardial dysfunction and adverse outcome in sepsis: an observational cohort study.BMC infectious diseases · 2024Observational
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Cardiomyopathy frequently complicates sepsis and is associated with increased mortality. Increased cardiac oxidative stress and mitochondrial dysfunction have been observed during sepsis, but the mechanisms responsible for these abnormalities have not been determined. We hypothesized that NADPH oxidase 2 (NOX2) activation could be responsible for sepsis-induced oxidative stress and cardiomyopathy. Treatment of isolated adult mouse cardiomyocytes with low concentrations of the endotoxin lipopolysaccharide (LPS) increased total cellular reactive oxygen species (ROS) and mitochondrial superoxide. Elevated mitochondrial superoxide was accompanied by depolarization of the mitochondrial inner membrane potential, an indication of mitochondrial dysfunction, and mitochondrial calcium overload. NOX2 inhibition decreased LPS-induced superoxide and prevented mitochondrial dysfunction. Further, cardiomyocytes from mice with genetic ablation of NOX2 did not have LPS-induced superoxide or mitochondrial dysfunction. LPS decreased contractility and calcium transient amplitude in isolated cardiomyocytes, and these abnormalities were prevented by inhibition of NOX2. LPS decreased systolic function in mice, measured by echocardiography. NOX2 inhibition was cardioprotective in 2 mouse models of sepsis, preserving systolic function after LPS injection or cecal ligation and puncture (CLP). These data show that inhibition of NOX2 decreases oxidative stress, preserves intracellular calcium handling and mitochondrial function, and alleviates sepsis-induced systolic dysfunction in vivo. Thus, NOX2 is a potential target for pharmacotherapy of sepsis-induced cardiomyopathy.
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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.