ArticleProceedings of the National Academy of Sciences of the United States of America2007
Genetic deletion of p66(Shc) adaptor protein prevents hyperglycemia-induced endothelial dysfunction and oxidative stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 246 citations in OpenAlex.
- Intensive glucose lowering and cardiovascular disease prevention in diabetes: reconciling the recent clinical trial data.Circulation · 2010Pooled it
- Article
- Therapeutic potential of MitoQ, a mitochondria-targeted antioxidant, in age-related physiological dysfunction.GeroScience · 2026Review
- Effects of Metformin Treatment Against Endometrial Cancer Cells Cultured In Vitro or Grafted into Female Balb/C Nude Mice: Insights into Cell Response and IGF-1R and PI3K/AKT/mTOR Signaling Pathways.Cell biochemistry and biophysics · 2025Article
- Protective Role of p66Shc Deletion in Physiological Renal Aging: Effects on G Protein-Coupled Receptor 124 Expression and Associated Cellular Senescence.International journal of molecular sciences · 2025Article
- The Impact of Glycaemic Variability on Vascular Dysfunction in Diabetes.Biomolecules · 2025Review
- How Can Molecules Induce Hemorrhoids? The Role of Genetics and Epigenetics in Hemorrhoidal Disease.International journal of molecular sciences · 2025Review
- Application and progress of 3D printed biomaterials in osteoporosis.Frontiers in bioengineering and biotechnology · 2025Review
- p66shc deficiency attenuates high glucose-induced autophagy dysfunction in Schwann cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- In diabetic male Wistar rats, quercetin-conjugated superparamagnetic iron oxide nanoparticles have an effect on the SIRT1/p66Shc-mediated pathway related to cognitive impairment.BMC pharmacology & toxicology · 2023Article
- The p66International journal of molecular sciences · 2023Review
- Mitochondria and Oxidative Stress as a Link between Alzheimer's Disease and Diabetes Mellitus.International journal of molecular sciences · 2023Review
- Mitochondria in endothelial cells angiogenesis and function: current understanding and future perspectives.Journal of translational medicine · 2023Review
- Novel Strategies in the Early Detection and Treatment of Endothelial Cell-Specific Mitochondrial Dysfunction in Coronary Artery Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Targeting SIRT1 Rescues Age- and Obesity-Induced Microvascular Dysfunction in Ex Vivo Human Vessels.Circulation research · 2022Article
- p66Shc in Cardiovascular Pathology.Cells · 2022Review
- Mitochondrial and metabolic dysfunction in ageing and age-related diseases.Nature reviews. Endocrinology · 2022Review
- The Role of p66Shc in Diabetes: A Comprehensive Review from Bench to Bedside.Journal of diabetes research · 2022Review
- Therapeutic potential of targeting oxidative stress in diabetic cardiomyopathy.Free radical biology & medicine · 2021Review
- The Role of Oxidative Stress in Cardiovascular Aging and Cardiovascular Diseases.Life (Basel, Switzerland) · 2021Review
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased production of reactive oxygen species (ROS) and loss of endothelial NO bioavailability are key features of vascular disease in diabetes mellitus. The p66(Shc) adaptor protein controls cellular responses to oxidative stress. Mice lacking p66(Shc) (p66(Shc-/-)) have increased resistance to ROS and prolonged life span. The present work was designed to investigate hyperglycemia-associated changes in endothelial function in a model of insulin-dependent diabetes mellitus p66(Shc-/-) mouse. p66(Shc-/-) and wild-type (WT) mice were injected with citrate buffer (control) or made diabetic by an i.p. injection of 200 mg of streptozotocin per kg of body weight. Streptozotocin-treated p66(Shc-/-) and WT mice showed a similar increase in blood glucose. However, significant differences arose with respect to endothelial dysfunction and oxidative stress. WT diabetic mice displayed marked impairment of endothelium-dependent relaxations, increased peroxynitrite (ONOO(-)) generation, nitrotyrosine expression, and lipid peroxidation as measured in the aortic tissue. In contrast, p66(Shc-/-) diabetic mice did not develop these high-glucose-mediated abnormalities. Furthermore, protein expression of the antioxidant enzyme heme oxygenase 1 and endothelial NO synthase were up-regulated in p66(Shc-/-) but not in WT mice. We report that p66(Shc-/-) mice are resistant to hyperglycemia-induced, ROS-dependent endothelial dysfunction. These data suggest that p66(Shc) adaptor protein is part of a signal transduction pathway relevant to hyperglycemia vascular damage and, hence, may represent a novel therapeutic target against diabetic vascular complications.
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.