ArticleAntioxidants & redox signaling2013
HNO enhances SERCA2a activity and cardiomyocyte function by promoting redox-dependent phospholamban oligomerization.
Article in Antioxidants & redox signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 77 citations in OpenAlex.
- A Phase 1 Randomized Study of Single Intravenous Infusions of the Novel Nitroxyl Donor BMS-986231 in Healthy Volunteers.Journal of clinical pharmacology · 2019Trial
- A Phase 2a dose-escalation study of the safety, tolerability, pharmacokinetics and haemodynamic effects of BMS-986231 in hospitalized patients with heart failure with reduced ejection fraction.European journal of heart failure · 2017Trial
- Nitroxyl (HNO): A novel approach for the acute treatment of heart failure.Circulation. Heart failure · 2013Trial
- Oxidative protein folding and CaCellular and molecular life sciences : CMLS · 2026Review
- The Landscape of SERCA2 in Cardiovascular Diseases: Expression Regulation, Therapeutic Applications, and Emerging Roles.Biomolecules · 2026Review
- Protective role of triiodothyronine in sepsis‑induced cardiomyopathy through phospholamban downregulation.International journal of molecular medicine · 2025Article
- Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Nitroxyl protects H9C2 cells from H/R-induced damage and inhibits autophagy via PI3K/Akt/mTOR pathway.PloS one · 2025Article
- Nitric Oxide in Biomaterial-Based Therapies for Coronary Heart Disease: Mechanistic Insights, Current Advances, and Translational Prospects.Biomaterials research · 2025Review
- Diabetes-induced chronic heart failure is due to defects in calcium transporting and regulatory contractile proteins: cellular and molecular evidence.Heart failure reviews · 2023Review
- The Chemical Biology of NO that Regulates Oncogenic Signaling and Metabolism: NOS2 and Its Role in Inflammatory Disease.Critical reviews in oncogenesis · 2023Review
- Targeting calcium regulators as therapy for heart failure: focus on the sarcoplasmic reticulum Ca-ATPase pump.Frontiers in cardiovascular medicine · 2023Review
- ER stress and calcium-dependent arrhythmias.Frontiers in physiology · 2022Review
- Regulation of Cardiac PKA Signaling by cAMP and Oxidants.Antioxidants (Basel, Switzerland) · 2021Review
- Cardiovascular Therapeutic Potential of the Redox Siblings, Nitric Oxide (NO•) and Nitroxyl (HNO), in the Setting of Reactive Oxygen Species Dysregulation.Handbook of experimental pharmacology · 2021Review
- Interaction among Hydrogen Sulfide and Other Gasotransmitters in Mammalian Physiology and Pathophysiology.Advances in experimental medicine and biology · 2021Review
- Article
- Sarcolipin Exhibits Abundant RNA Transcription and Minimal Protein Expression in Horse Gluteal Muscle.Veterinary sciences · 2020Article
- Receptor-independent modulation of cAMP-dependent protein kinase and protein phosphatase signaling in cardiac myocytes by oxidizing agents.The Journal of biological chemistry · 2020Article
- Heart Plasticity in Response to Pressure- and Volume-Overload: A Review of Findings in Compensated and Decompensated Phenotypes.Frontiers in physiology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
aimsNitroxyl (HNO) interacts with thiols to act as a redox-sensitive modulator of protein function. It enhances sarcoplasmic reticular Ca(2+) uptake and myofilament Ca(2+) sensitivity, improving cardiac contractility. This activity has led to clinical testing of HNO donors for heart failure. Here we tested whether HNO alters the inhibitory interaction between phospholamban (PLN) and the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) in a redox-dependent manner, improving Ca(2+) handling in isolated myocytes/hearts.
resultsVentriculocytes, sarcoplasmic reticulum (SR) vesicles, and whole hearts were isolated from control (wildtype [WT]) or PLN knockout (pln(-/-)) mice. Compared to WT, pln(-/-) myocytes displayed enhanced resting sarcomere shortening, peak Ca(2+) transient, and blunted β-adrenergic responsiveness. HNO stimulated shortening, relaxation, and Ca(2+) transient in WT cardiomyocytes, and evoked positive inotropy/lusitropy in intact hearts. These changes were markedly blunted in pln(-/-) cells/hearts. HNO enhanced SR Ca(2+) uptake in WT but not pln(-/-) SR-vesicles. Spectroscopic studies in insect cell microsomes expressing SERCA2a±PLN showed that HNO increased Ca(2+)-dependent SERCA2a conformational flexibility but only when PLN was present. In cardiomyocytes, HNO achieved this effect by stabilizing PLN in an oligomeric disulfide bond-dependent configuration, decreasing the amount of free inhibitory monomeric PLN available. INNOVATION: HNO-dependent redox changes in myocyte PLN oligomerization relieve PLN inhibition of SERCA2a.
conclusionsPLN plays a central role in HNO-induced enhancement of SERCA2a activity, leading to increased inotropy/lusitropy in intact myocytes and hearts. PLN remains physically associated with SERCA2a; however, less monomeric PLN is available resulting in decreased inhibition of the enzyme. These findings offer new avenues to improve Ca(2+) handling in failing hearts.
Indexed as
Identifiers
What OpenQuestion holds
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.