ArticleCardiovascular research2013
Defective Nrf2-dependent redox signalling contributes to microvascular dysfunction in type 2 diabetes.
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 39 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
39 citing papers in PubMed, 75 citations in OpenAlex.
- Redox Regulation of Microvascular Physiology and Pathophysiology: Insights into Therapeutic Strategies and Limitations.Antioxidants & redox signaling · 2025Review
- Molecular signatures of disulfidptosis: interplay with programmed cell death pathways and therapeutic implications in oncology.Cellular & molecular biology letters · 2025Review
- Oxidative stress and NRF2 signaling in kidney injury.Toxicological research · 2025Review
- EPAS1 Attenuates Atherosclerosis Initiation at Disturbed Flow Sites Through Endothelial Fatty Acid Uptake.Circulation research · 2024Article
- Disulfide stress and its role in cardiovascular diseases.Redox biology · 2024Review
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- Aerobic exercise improves BKActa diabetologica · 2024Article
- Inhibition effect of copper-bearing metals on arterial neointimal hyperplasia via the AKT/Nrf2/ARE pathwayRegenerative biomaterials · 2024Article
- Transient receptor potential vanilloid type 1: cardioprotective effects in diabetic models.Channels (Austin, Tex.) · 2023Review
- Diabetic cardiomyopathy: a brief summary on lipid toxicity.ESC heart failure · 2023Review
- Mechanisms of Vascular CaHandbook of experimental pharmacology · 2023Article
- Cinnamaldehyde Supplementation Reverts Endothelial Dysfunction in Rat Models of Diet-Induced Obesity: Role of NF-E2-Related Factor-2.Antioxidants (Basel, Switzerland) · 2022Article
- Oxidative Regulation of Vascular CaAntioxidants (Basel, Switzerland) · 2022Review
- NRF2 and Diabetes: The Good, the Bad, and the Complex.Diabetes · 2022Review
- Cardiac NF-κB Acetylation Increases While Nrf2-Related Gene Expression and Mitochondrial Activity Are Impaired during the Progression of Diabetes in UCD-T2DM Rats.Antioxidants (Basel, Switzerland) · 2022Article
- Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases.International journal of molecular sciences · 2022Review
- Therapeutic potential of targeting oxidative stress in diabetic cardiomyopathy.Free radical biology & medicine · 2021Review
- Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens.Antioxidants (Basel, Switzerland) · 2021Article
- Cellular and molecular effects of hyperglycemia on ion channels in vascular smooth muscle.Cellular and molecular life sciences : CMLS · 2021Review
- Antioxidant supplements and endurance exercise: Current evidence and mechanistic insights.Redox biology · 2020Review
Corrections and comments
- Commented on by
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
aimsIn type 2 diabetes, antioxidant depletion contributes to increased oxidative stress in the microvasculature. The current study was designed to assess how oxidative stress contributes to functional changes in the microvasculature, and determine the importance, and the effects of pharmacologically targeting, the transcription factor Nrf2. METHODS AND
resultsPressure myography was used to measure myogenic constriction in mesenteric arterioles from diabetic (db/db) and non-diabetic (db/m) mice. Compared with db/m, myogenic constriction was larger in db/db, independent of the endothelial cell layer, and directly correlated with elevated basal and pressure-induced reactive oxygen species (ROS) production. Nrf2 was depleted in db/db vessels and associated with down-regulation of Nrf2-regulated genes. Notably, expression of GCLC and GCLM, enzymes important for glutathione (GSH) synthesis, was dramatically reduced, as was total cellular GSH. Normal myogenic function was restored to db/db arterioles by incubation with cell-permeant GSH. Similarly, the db/db myogenic phenotype was recapitulated in the db/m vessels by pharmacological GSH depletion. Treatment with the Nrf2-activator sulforaphane increased Nrf2 and promoted its nuclear localization and increased GCLC and GCLM expression in both db/m and db/db. Sulforaphane dramatically lowered ROS signalling in db/db and reduced myogenic tone to levels similar to that seen in db/m vessels.
conclusionDepleted Nrf2 and expression of its dependent genes compromises antioxidant capacity resulting in dysfunctional myogenic tone in diabetes that is reversed by the Nrf2-activator sulforaphane.
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.