ArticleDiabetes2010
Increased cytochrome P4502E1 expression and altered hydroxyeicosatetraenoic acid formation mediate diabetic vascular dysfunction: rescue by guanylyl-cyclase activation.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- Targeting tRNA-Derived Non-Coding RNA Alleviates Diabetes-Induced Visual Impairment through Protecting Retinal Neurovascular Unit.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Inflammation as a therapeutic target in heart failure with preserved ejection fraction.Frontiers in cardiovascular medicine · 2023Review
- Cytochrome P450 CYP2E1 Suppression Ameliorates Cerebral Ischemia Reperfusion Injury.Antioxidants (Basel, Switzerland) · 2021Article
- Impact of cigarette smoking on nitric oxide-sensitive and nitric oxide-insensitive soluble guanylate cyclase-mediated vascular tone regulation.Hypertension research : official journal of the Japanese Society of Hypertension · 2020Article
- Conditional deletion of smooth muscle Cullin-3 causes severe progressive hypertension.JCI insight · 2019Article
- Review
- Effect of chronic uremia on the transcriptional profile of the calcified aorta analyzed by RNA sequencing.American journal of physiology. Renal physiology · 2016Article
- Alcohol Upregulation of CYP2A5: Role of Reactive Oxygen Species.Reactive oxygen species (Apex, N.C.) · 2016Article
- Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1.Current drug metabolism · 2015Review
- Identification of genes whose expression is altered by obesity throughout the arterial tree.Physiological genomics · 2014Article
- Identification of 2-piperidone as a biomarker of CYP2E1 activity through metabolomic phenotyping.Toxicological sciences : an official journal of the Society of Toxicology · 2013Article
- Warfarin and acetaminophen interaction: a summary of the evidence and biologic plausibility.Blood · 2011Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveWe investigated the mechanisms underlying vascular endothelial and contractile dysfunction in diabetes as well as the effect of HMR1766, a novel nitric oxide (NO)-independent activator of soluble guanylyl cyclase (sGC). RESEARCH DESIGN AND
methodsTwo weeks after induction of diabetes by streptozotocin, Wistar rats received either placebo or HMR1766 (10 mg/kg twice daily) for another 2 weeks; thereafter, vascular function was assessed.
resultsEndothelial function and contractile responses were significantly impaired, while vascular superoxide formation was increased in the aortae from diabetic versus healthy control rats. Using RNA microarrays, cytochrome P4502E1 (CYP2E1) was identified as the highest upregulated gene in diabetic aorta. CYP2E1 protein was significantly increased (16-fold) by diabetes, leading to a reduction in levels of the potent vasoconstrictor 20-hydroxy-eicosatetraenoic acid (20-HETE). Induction of CYP2E1 expression in healthy rats using isoniazide mimicked the diabetic noncontractile vascular response while preincubation of aortae from STZ-diabetic rats in vitro with 20-HETE rescued contractile function. Chronic treatment with the sGC activator HMR1766 improved NO sensitivity and endothelial function, reduced CYP2E1 expression and superoxide formation, enhanced 20-HETE levels, and reversed the contractile deficit observed in the diabetic rats that received placebo.
conclusionsUpregulation of CYP2E1 is essentially involved in diabetic vascular dysfunction. Chronic treatment with the sGC activator HMR1766 reduced oxidative stress, decreased CYP2E1 levels, and normalized vasomotor function in diabetic rats.
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