ArticleAmerican journal of physiology. Heart and circulatory physiology2015
N-acetylcysteine reverses diastolic dysfunction and hypertrophy in familial hypertrophic cardiomyopathy.
Article in American journal of physiology. Heart and circulatory physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Implications of S-glutathionylation of sarcomere proteins in cardiac disorders, therapies, and diagnosis.Frontiers in cardiovascular medicine · 2022Pooled it
- Hypertrophy Regression With N-Acetylcysteine in Hypertrophic Cardiomyopathy (HALT-HCM): A Randomized, Placebo-Controlled, Double-Blind Pilot Study.Circulation research · 2018Trial
- Evidence for a role of adverse sarcomere signaling in atrial fibrillation induction.Journal of molecular and cellular cardiology plus · 2026Review
- Venous vascular pharmacology: how does it contribute to heart failure with preserved ejection fraction?European heart journal. Cardiovascular pharmacotherapy · 2026Review
- SGLT2 Inhibitors in Hypertrophic Cardiomyopathy: Emerging Evidence and Putative Mechanisms.Biomolecules · 2026Review
- In-depth characterization of S-glutathionylation in ventricular myosin light chain 1 across species by top-down proteomics.Journal of molecular and cellular cardiology · 2025Article
- Exploration of calcium and amino acids for children with primary cardiomyopathies based on genetic characteristics.Frontiers in pediatrics · 2025Article
- Genetic Mutations and Mitochondrial Redox Signaling as Modulating Factors in Hypertrophic Cardiomyopathy: A Scoping Review.International journal of molecular sciences · 2024Article
- Advances in the Use ofAntioxidants (Basel, Switzerland) · 2023Review
- Mechano-energetic uncoupling in hypertrophic cardiomyopathy: Pathophysiological mechanisms and therapeutic opportunities.Journal of molecular and cellular cardiology plus · 2023Review
- Altered coronary artery function, arteriogenesis and endothelial YAP signaling in postnatal hypertrophic cardiomyopathy.Frontiers in physiology · 2023Article
- Targeting lipid metabolism as a new therapeutic strategy for inherited cardiomyopathies.Frontiers in cardiovascular medicine · 2023Review
- Oral N-acetylcysteine as an adjunct to standard medical therapy improved heart function in cases with stable class II and III systolic heart failure.Irish journal of medical science · 2022Article
- Review
- Article
- Pushing the Limits of Medical Management in HCM: A Review of Current Pharmacological Therapy Options.International journal of molecular sciences · 2021Review
- Nutraceutical, Dietary, and Lifestyle Options for Prevention and Treatment of Ventricular Hypertrophy and Heart Failure.International journal of molecular sciences · 2021Review
- Article
- Unraveling the Genotype-Phenotype Relationship in Hypertrophic Cardiomyopathy: Obesity-Related Cardiac Defects as a Major Disease Modifier.Journal of the American Heart Association · 2020Review
- Mitochondrial Energetics and Ca2Journal of clinical medicine · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
S-glutathionylation of cardiac myosin-binding protein C (cMyBP-C) induces Ca(2+) sensitization and a slowing of cross-bridge kinetics as a result of increased oxidative signaling. Although there is evidence for a role of oxidative stress in disorders associated with hypertrophic cardiomyopathy (HCM), this mechanism is not well understood. We investigated whether oxidative myofilament modifications may be in part responsible for diastolic dysfunction in HCM. We administered N-acetylcysteine (NAC) for 30 days to 1-mo-old wild-type mice and to transgenic mice expressing a mutant tropomyosin (Tm-E180G) and nontransgenic littermates. Tm-E180G hearts demonstrate a phenotype similar to human HCM. After NAC administration, the morphology and diastolic function of Tm-E180G mice was not significantly different from controls, indicating that NAC had reversed baseline diastolic dysfunction and hypertrophy in our model. NAC administration also increased sarco(endo)plasmic reticulum Ca(2+) ATPase protein expression, reduced extracellular signal-related kinase 1/2 phosphorylation, and normalized phosphorylation of phospholamban, as assessed by Western blot. Detergent-extracted fiber bundles from NAC-administered Tm-E180G mice showed nearly nontransgenic (NTG) myofilament Ca(2+) sensitivity. Additionally, we found that NAC increased tension cost and rate of cross-bridge reattachment. Tm-E180G myofilaments were found to have a significant increase in S-glutathionylation of cMyBP-C, which was returned to NTG levels upon NAC administration. Taken together, our results indicate that oxidative myofilament modifications are an important mediator in diastolic function, and by relieving this modification we were able to reverse established diastolic dysfunction and hypertrophy in HCM.
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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.