ArticleCardiovascular research2013
Nrf2 deficiency prevents reductive stress-induced hypertrophic cardiomyopathy.
Article in Cardiovascular research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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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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Who cites it
58 citing papers in PubMed, 98 citations in OpenAlex.
- The emerging role of Nrf2 in heart failure: From cardioprotection to therapeutic approaches.ESC heart failure · 2025Review
- Reductive stress: The key pathway in metabolic disorders induced by overnutrition.Journal of advanced research · 2025Review
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- Approaches toAnimal reproduction · 2025Article
- Dimethyl Fumarate Prevents the Development of Chronic Social Stress-Induced Hypertension in Borderline Hypertensive Rats.Antioxidants (Basel, Switzerland) · 2024Article
- Exploratory bibliometric analysis and text mining to reveal research trends in cardiac aging.Aging medicine (Milton (N.S.W)) · 2024Article
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- Sleep fragmentation induces heart failure in a hypertrophic cardiomyopathy mouse model by altering redox metabolism.iScience · 2024Article
- The Contribution of the Nrf2/ARE System to Mechanotransduction in Musculoskeletal and Periodontal Tissues.International journal of molecular sciences · 2023Review
- Persistent activation of Nrf2 in a p62-dependent non-canonical manner aggravates lead-induced kidney injury by promoting apoptosis and inhibiting autophagy.Journal of advanced research · 2023Article
- Insights into the Molecular Mechanisms of NRF2 in Kidney Injury and Diseases.International journal of molecular sciences · 2023Review
- Interplay between Nrf2 and αB-crystallin in the lens and heart of zebrafish under proteostatic stress.Frontiers in molecular biosciences · 2023Article
- The bridge between cell survival and cell death: reactive oxygen species-mediated cellular stress.EXCLI journal · 2023Review
- Transgenic Expression of Nrf2 Induces a Pro-Reductive Stress and Adaptive Cardiac Remodeling in the Mouse.Genes · 2022Article
- The role of glutathione peroxidase-1 in health and disease.Free radical biology & medicine · 2022Review
- Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls.Antioxidants (Basel, Switzerland) · 2022Review
- Targeting the NRF2/HO-1 Antioxidant Pathway in FLT3-ITD-Positive AML Enhances Therapy Efficacy.Antioxidants (Basel, Switzerland) · 2022Article
- Cigarette smoke-induced oxidative stress activates NRF2 to mediate fibronectin disorganization in vascular formation.Open biology · 2022Article
- Oxidative Stress in Arterial Hypertension (HTN): The Nuclear Factor Erythroid Factor 2-Related Factor 2 (Nrf2) Pathway, Implications and Future Perspectives.Pharmaceutics · 2022Review
- Tandem Mass Tagging Based Identification of Proteome Signatures for Reductive Stress Cardiomyopathy.Frontiers in cardiovascular medicine · 2022Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
aimsMutant protein aggregation (PA) cardiomyopathy (MPAC) is characterized by reductive stress (RS), PA (of chaperones and cytoskeletal components), and ventricular dysfunction in transgenic mice expressing human mutant CryAB (hmCryAB). Sustained activation of nuclear erythroid-2 like factor-2 (Nrf2) causes RS, which contributes to proteotoxic cardiac disease. The goals of this pre-clinical study were to (i) investigate whether disrupting Nrf2-antioxidant signalling prevents RS and rescues redox homeostasis in hearts expressing the mutant chaperone and (ii) elucidate mechanisms that could delay proteotoxic cardiac disease. METHODS AND
resultsNon-transgenic (NTG), transgenic (TG) with MPAC and MPAC-TG:Nrf2-deficient (Nrf2-def) mice were used in this study. The effects of Nrf2 diminution (Nrf2±) on RS mediated MPAC in TG mice were assessed at 6-7 and 10 months of age. The diminution of Nrf2 prevented RS and prolonged the survival of TG mice (∼50 weeks) by an additional 20-25 weeks. The TG:Nrf2-def mice did not exhibit cardiac hypertrophy at even 60 weeks, while the MPAC-TG mice developed pathological hypertrophy and heart failure starting at 24-28 weeks of age. Aggregation of cardiac proteins was significantly reduced in TG:Nrf2-def when compared with TG mice at 7 months. Preventing RS and maintaining redox homeostasis in the TG:Nrf2-def mice ameliorated PA, leading to decreased ubiquitination of proteins.
conclusionNrf2 deficiency rescues redox homeostasis, which reduces aggregation of mutant proteins, thereby delaying the proteotoxic pathological cardiac remodelling caused by RS and toxic protein aggregates.
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