The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Deletion of p66 shc Gene Protects Against Age-Related Endothelial Dysfunction
Open accessAbstract
Background— Enhanced production of reactive oxygen species (ROS) has been recognized as the major determinant of age-related endothelial dysfunction. The p66 shc protein controls cellular responses to oxidative stress. Mice lacking p66 shc (p66 shc−/− ) have increased resistance to ROS and a 30% prolonged life span. The present study investigates age-dependent changes of endothelial function in this model. Methods and Results— Aortic rings from young and old p66 shc−/− or wild-type (WT) mice were suspended for isometric tension recording. Nitric oxide (NO) release was measured by a porphyrinic microsensor. Expression of endothelial NO synthase (eNOS), inducible NOS (iNOS), superoxide dismutase, and nitrotyrosine-containing proteins was assessed by Western blotting. Nitrotyrosine residues were also identified by immunohistochemistry. Superoxide (O 2 − ) production was determined by coelenterazine-enhanced chemiluminescence. Endothelium-dependent relaxation in response to acetylcholine was age-dependently impaired in WT mice but not in p66 shc−/− mice. Accordingly, an age-related decline of NO release was found in WT but not in p66 shc−/− mice. The expression of eNOS and manganese superoxide dismutase was not affected by aging either in WT or in p66 shc−/− mice, whereas iNOS was upregulated only in old WT mice. It is interesting that old WT mice displayed a significant increase of O 2 − production as well as of nitrotyrosine expression compared with young animals. Such age-dependent changes were not found in p66 shc−/− mice. Conclusions— We report that inactivation of the p66 shc gene protects against age-dependent, ROS-mediated endothelial dysfunction. These findings suggest that the p66 shc is part of a signal transduction pathway also relevant to endothelial integrity and may represent a novel target to prevent vascular aging.
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“Mutant p66Shc−/− mice have been reported to be resistant to oxidative stress and to have an increased lifespan185, as well as reduced age-dependent endothelial dysfunction186.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [186]
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“recent evidence suggests that mitochondrial dysfunction may play an important role in large elastic artery stiffening and endothelial dysfunction with aging via modulation of oxidative stress (33, 35, 56, 198).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [56]
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The p66shc adaptor protein controls oxidative stress response and life span in mammals
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Self-citationEnhanced Peroxynitrite Formation Is Associated with Vascular Aging
van der Loo, B., Labugger, R., Skepper, J. N., Bachschmid, M. M., Kilo, J., Powell, J. M., Palacios‐Callender, M., Erusalimsky, J. D., Quaschning, T., Maliñski, T., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.12.1731 · Cited by 684
Self-citationAge-Related Reduction of NO Availability and Oxidative Stress in Humans
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Aging-Induced Phenotypic Changes and Oxidative Stress Impair Coronary Arteriolar Function
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Mapping and Ablation of Ventricular Fibrillation Associated With Long-QT and Brugada Syndromes
Haı̈ssaguerre, M., Extramiana, F., Hocini, M., CAUCHEMEZ, B., Jaı̈s, P., Cabrera, J. Á., Farre, G., Leenhardt, A., Sanders, P., Scavée, C., et al. (2003) · Circulation · doi:10.1161/01.cir.0000088781.99943.95 · Cited by 518
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Nitric Oxide and Peroxynitrite in Health and Disease
Pacher, P., Beckman, J. S., & Liaudet, L. (2007) · Physiological Reviews · doi:10.1152/physrev.00029.2006 · Cited by 6,390
Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals?
Giorgio, M., Trinei, M., Migliaccio, E., & Pelicci, P. G. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2240 · Cited by 1,473
Self-citationCysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery
Paulsen, C. E., & Carroll, K. S. (2013) · Chemical Reviews · doi:10.1021/cr300163e · Cited by 1,313
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“…et al., 1999; Trinei et al., 2002). t Intracellular ROS levels are decreased in p66Shc−/− m cells, as revealed by the reduced oxidation of ROS-senc sitive probes and the reduced accumulation of endogeR nous markers of oxidative stress (8-oxo-guanosine) i(Trinei et al., 2002; Francia et al., 2004).”
Self-citationMitochondrial and metabolic dysfunction in ageing and age-related diseases
Amorim, J. A., Coppotelli, G., Rolo, A. P., Palmeira, C. M., Ross, J. M., & Sinclair, D. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00626-7 · Cited by 990
Metadata
- Authors
- Francia, P., delli Gatti, C., Bachschmid, M., Martin-Padura, I., Savoia, C., Migliaccio, E., Pelicci, P. G., Schiavoni, M., Lüscher, T. F., Volpe, M., & Cosentino, F.
- Affiliations
- University of Konstanz (DE)
- From Cardiovascular Research & Cardiology, Institute of Physiology, Zürich, Irchel and University Hospital, Zürich, Switzerland (P.F., C.D.G., M.S., T.F.L., F.C.); Division of Cardiology, 2nd Faculty of Medicine, University “La Sapienza,” Rome, and IRCCS Neuromed, Pozzilli (IS), Italy (P.F., C.S., M.V., F.C.); Department of Biology, University of Konstanz, Germany (M.B.); and Department of Experimental Oncology of the European Institute of Oncology, Milan, Italy (I.M.-P., E.M., P.G.P.).
- ORCID
- Venue
- Circulation
- Published
- 2004-11-02
- Volume
- 110
- Issue
- 18
- Pages
- 2889-2895
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2101209889
- Semantic Scholar
- 3f117729d32b45e441d1ca919d8085736409dd05
- Cited by
- 298
- References
- 29
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 6 · 2023: 6 · 2022: 9 · 2021: 13 · 2020: 15 · 2019: 13 · 2018: 14 · 2017: 11 · 2016: 14 · 2015: 10 · 2014: 17 · 2013: 20 · 2012: 18
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Update notices
- correction (2005-01-25)
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- Circulation (publishedVersion, public-domain)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- National Research Foundation
- Schweizerische Herzstiftung
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- p66Shc, endothelial dysfunction, vascular aging, reactive oxygen species, oxidative stress, nitric oxide, nitrotyrosine, superoxide production, endothelial nitric oxide synthase, inducible nitric oxide synthase, superoxide dismutase, acetylcholine-induced relaxation, knockout mice
- MeSH terms
- Src Homology 2 Domain-Containing, Transforming Protein 1, Aging, Animals, Aorta, Endothelium, Vascular, Isometric Contraction, Longevity, Male, Nitric Oxide, Proteins, Superoxide Dismutase, Tyrosine, Vasoconstriction, Reactive Oxygen Species, Mice, Knockout, Oxidative Stress, Nitric Oxide Synthase, Adaptor Proteins, Signal Transducing, Mice, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, Shc Signaling Adaptor Proteins
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