ArticleAmerican journal of physiology. Heart and circulatory physiology2016
The NRF2 knockout rat: a new animal model to study endothelial dysfunction, oxidant stress, and microvascular rarefaction.
Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 70 citations in OpenAlex.
- Apocynin and Tempol ameliorate dietary sodium-induced declines in cutaneous microvascular function in salt-resistant humans.American journal of physiology. Heart and circulatory physiology · 2019Trial
- NRF2 deficit prevents pathologic Tau seeding and spreading in an induced tauopathy mouse model.Redox biology · 2026Article
- Inhibition of smooth muscle phenotypic modulation by bardoxolone methyl, omaveloxolone, and cinnamaldehyde is Nrf-2 dependent.Advances in redox research · 2026Article
- Redox Regulation of Microvascular Physiology and Pathophysiology: Insights into Therapeutic Strategies and Limitations.Antioxidants & redox signaling · 2025Review
- The glutathione-dependent neuroprotective activity of the blood-CSF barrier is inducible through the Nrf2 signaling pathway during postnatal development.Fluids and barriers of the CNS · 2025Article
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Isoflavones Effects on Vascular and Endothelial Outcomes: How Is the Gut Microbiota Involved?Pharmaceuticals (Basel, Switzerland) · 2024Review
- Quantitative proteomic analyses uncover regulatory roles of Nrf2 in human endothelial cells.Cell stress & chaperones · 2023Article
- Severe heat stress modulated nuclear factor erythroid 2-related factor 2 and macrophage migration inhibitory factor pathway in rat liver.Journal of cell communication and signaling · 2022Article
- Effects of Antioxidant Gene Overexpression on Stress Resistance and Malignization In Vitro and In Vivo: A Review.Antioxidants (Basel, Switzerland) · 2022Review
- Multisystem involvement, defective lysosomes and impaired autophagy in a novel rat model of nephropathic cystinosis.Human molecular genetics · 2022Article
- Antioxidant Polyphenols ofAntioxidants (Basel, Switzerland) · 2022Article
- Recent Advances in the Production of Genome-Edited Rats.International journal of molecular sciences · 2022Review
- Study on the Local Anti-Osteoporosis Effect of Polaprezinc-Loaded Antioxidant Electrospun Membrane.International journal of nanomedicine · 2022Article
- Potential Protective Effects of Equol (Soy Isoflavone Metabolite) on Coronary Heart Diseases-From Molecular Mechanisms to Studies in Humans.Nutrients · 2021Review
- NRF2 Activation and Downstream Effects: Focus on Parkinson's Disease and Brain Angiotensin.Antioxidants (Basel, Switzerland) · 2021Review
- Keap1/Nrf2 Signaling Pathway.Antioxidants (Basel, Switzerland) · 2021Article
- Association of Nuclear Factor Erythroid-2-Related Actor 2 Gene Polymorphisms with Diabetic Nephropathy in Chinese Patients.International journal of general medicine · 2021Article
- Targeting Transcription Factor Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) for the Intervention of Vascular Cognitive Impairment and Dementia.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- Biomimetics provides lessons from nature for contemporary ways to improve human health.Journal of clinical and translational science · 2021Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Nuclear factor (erythroid-derived 2)-like-2 (NRF2) is a master antioxidant and cell protective transcription factor that upregulates antioxidant defenses. In this study we developed a strain of Nrf2 null mutant rats to evaluate the role of reduced NRF2-regulated antioxidant defenses in contributing to endothelial dysfunction and impaired angiogenic responses during salt-induced ANG II suppression. Nrf2(-/-) mutant rats were developed using transcription activator-like effector nuclease technology in the Sprague-Dawley genetic background, and exhibited a 41-bp deletion that included the start codon for Nrf2 and an absence of immunohistochemically detectable NRF2 protein. Expression of mRNA for the NRF2-regulated indicator enzymes heme oxygenase-1, catalase, superoxide dismutase 1, superoxide dismutase 2, and glutathione reductase was significantly lower in livers of Nrf2(-/-) mutant rats fed high salt (HS; 4% NaCl) for 2 wk compared with wild-type controls. Endothelium-dependent dilation to acetylcholine was similar in isolated middle cerebral arteries (MCA) of Nrf2(-/-) mutant rats and wild-type littermates fed low-salt (0.4% NaCl) diet, and was eliminated by short-term (3 days) HS diet in both strains. Low-dose ANG II infusion (100 ng/kg sc) reversed salt-induced endothelial dysfunction in MCA and prevented microvessel rarefaction in wild-type rats fed HS diet, but not in Nrf2(-/-) mutant rats. The results of this study indicate that suppression of NRF2 antioxidant defenses plays an essential role in the development of salt-induced oxidant stress, endothelial dysfunction, and microvessel rarefaction in normotensive rats and emphasize the potential therapeutic benefits of directly upregulating NRF2-mediated antioxidant defenses to ameliorate vascular oxidant stress in humans.
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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.