ArticleStroke2013
Deficient eNOS phosphorylation is a mechanism for diabetic vascular dysfunction contributing to increased stroke size.
Article in Stroke, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Therapeutic potential of nitric oxide and its donors in hemorrhagic and ischemic stroke: a systematic review.Medical gas research · 2026Pooled it
- Impact of Endothelial Diversity and Dysfunction on Cardiovascular Disease.Comprehensive Physiology · 2025Review
- Glucose transporter 1 is essential to maintain brain endothelial cell homeostasis under hyperglycemia condition.American journal of physiology. Cell physiology · 2025Article
- S-nitrosylation of EZH2 alters PRC2 assembly, methyltransferase activity, and EZH2 stability to maintain endothelial homeostasis.Nature communications · 2025Article
- Promotion of nitric oxide production: mechanisms, strategies, and possibilities.Frontiers in physiology · 2025Review
- Targeting hypoxia and thrombospondin-2 in diabetic wound healing.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Near-Infrared II Photobiomodulation Preconditioning Ameliorates Stroke Injury via Phosphorylation of eNOS.Stroke · 2024Article
- Reduced endothelial caveolin-1 underlies deficits in brain insulin signalling in type 2 diabetes.Brain : a journal of neurology · 2023Article
- Growth State-Dependent Activation of eNOS in Response to DHA: Involvement of p38 MAPK.International journal of molecular sciences · 2023Article
- Role of Terpenophenolics in Modulating Inflammation and Apoptosis in Cardiovascular Diseases: A Review.International journal of molecular sciences · 2023Review
- Physiological concentration of protocatechuic acid directly protects vascular endothelial function against inflammation in diabetes through Akt/eNOS pathway.Frontiers in nutrition · 2023Article
- Photobiomodulation and nitric oxide signaling.Nitric oxide : biology and chemistry · 2023Review
- Dietary Blueberry Ameliorates Vascular Complications in Diabetic Mice Possibly through NOX4 and Modulates Composition and Functional Diversity of Gut Microbes.Molecular nutrition & food research · 2022Article
- Protein kinase N2 mediates flow-induced endothelial NOS activation and vascular tone regulation.The Journal of clinical investigation · 2021Article
- Cerebral arterial architectonics and CFD simulation in mice with type 1 diabetes mellitus of different duration.Scientific reports · 2021Article
- Biological Activity of c-Peptide in Microvascular Complications of Type 1 Diabetes-Time for Translational Studies or Back to the Basics?International journal of molecular sciences · 2020Review
- Endothelial nitric oxide synthase-derived nitric oxide in the regulation of metabolism.F1000Research · 2020Review
- Inhibition of acid sphingomyelinase activity ameliorates endothelial dysfunction inBioscience reports · 2019Article
- Identification of AnnexinA1 as an Endogenous Regulator of RhoA, and Its Role in the Pathophysiology and Experimental Therapy of Type-2 Diabetes.Frontiers in immunology · 2019Article
- Endothelial NOS: perspective and recent developments.British journal of pharmacology · 2019Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
background and purposePhosphorylation of eNOS, an important post-translational modulator of its enzymatic activity, is reduced in diabetes mellitus. We hypothesized that modulation of eNOS phosphorylation could overcome diabetic vascular dysfunction and improves the outcome to stroke.
methodsWe used the db/db mouse model of type 2 diabetes mellitus. We mated db/db mice with eNOS knock-in mice that carry single amino acid mutations at the S1176 phosphorylation site; the phosphomimetic SD mutation (serine replaced by aspartate) shows increased eNOS enzymatic activity, whereas the unphosphorylatable SA mutation (serine replaced by alanine) shows decreased eNOS activity. We characterized the vascular anatomy, baseline physiological parameters, and vascular reactivity. We used the middle cerebral artery occlusion model of stroke and measured infarct volume and neurological deficits.
resultsdb/db mice showed diminished eNOS phosphorylation at S1176. eNOS SD and SA mutations do not change the vascular anatomy at the Circle of Willis, brain capillary density, heart rate, or arterial blood gases of db/db mice. The eNOS SD mutation, but not the SA mutation, lowers blood pressure and improves vascular reactivity to acetylcholine in db/db mice. The eNOS SD mutation reduces stroke size and neurological deficit after middle cerebral artery occlusion.
conclusionsDiminished eNOS phosphorylation is a mechanism of vascular dysfunction in db/db mice. We show here that modulation of the eNOS S1176 phosphorylation site in db/db mice is associated with improved vascular reactivity and improved outcome to stroke after middle cerebral artery occlusion.
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