The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Cellular glutathione peroxidase deficiency and endothelial dysfunction
Abstract
Cellular glutathione peroxidase (GPx-1) is the most abundant intracellular isoform of the GPx antioxidant enzyme family. In this study, we hypothesized that GPx-1 deficiency directly induces an increase in vascular oxidant stress, with resulting endothelial dysfunction. We studied vascular function in a murine model of homozygous deficiency of GPx-1 (GPx-1−/−). Mesenteric arterioles of GPx-1−/−mice demonstrated paradoxical vasoconstriction to β-methacholine and bradykinin, whereas wild-type (WT) mice showed dose-dependent vasodilation in response to both agonists. One week of treatment of GPx-1−/−mice withl-2-oxothiazolidine-4-carboxylic acid (OTC), which increases intracellular thiol pools, resulted in restoration of normal vascular reactivity in the mesenteric bed of GPx-1−/−mice. We observed an increase of the isoprostane iPF 2α-III, a marker of oxidant stress, in the plasma and aortas of GPx-1−/−mice compared with WT mice, which returned toward normal after OTC treatment. Aortic sections from GPx-1−/−mice showed increased binding of an anti-3-nitrotyrosine antibody in the absence of frank vascular lesions. These findings demonstrate that homozygous deficiency of GPx-1 leads to impaired endothelium-dependent vasodilator function presumably due to a decrease in bioavailable nitric oxide and to increased vascular oxidant stress. These vascular abnormalities can be attenuated by increasing bioavailable intracellular thiol pools.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“GPx-1-deficient mice manifest endothelial dysfunction, characterized by a lack of normal responses to endothelium-dependent vasoactive compounds (134, 135).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [135]
Citations
Cites
Atherosclerosis--an inflammatory disease
Ross, R. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901143400207 · Cited by 21,725
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704 · cited 1×
“NO plays a critical role in the endothelial response to muscarinic agonists (20).”
Background[12] Assays of glutathione peroxidase
Flohé, L., & Günzler, W. A. (1984) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(84)05015-1 · Cited by 4,954
Schächinger, V., Britten, M. B., & Zeiher, A. M. (2000) · Circulation · doi:10.1161/01.cir.101.16.1899 · Cited by 2,589
Long-Term Follow-Up of Patients With Mild Coronary Artery Disease and Endothelial Dysfunction
Suwaidi, J. M. S. A., Hamasaki, S., Higano, S. T., Nishimura, R. A., Holmes, D. R., & Lerman, A. (2000) · Circulation · doi:10.1161/01.cir.101.9.948 · Cited by 2,044
Rubbo, H., Radí, R., Trujillo, M., Telleri, R., Kalyanaraman, B., Barnes, S., KIRK, M. C., & Freeman, B. Α. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47160-8 · Cited by 1,350
[5] Diversity of glutathione peroxidases
Maiorino, F. M., Brigelius‐Flohé, R., Aumann, K. D., Roveri, A., Schomburg, D., & Flohé, L. (1995) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(95)52007-4 · Cited by 854
Davı̀, G., Ciabattoni, G., Consoli, A., Mezzetti, A., Falco, A., Santarone, S., Pennese, E., Vitacolonna, E., Bucciarelli, T., Costantini, F., et al. (1999) · Circulation · doi:10.1161/01.cir.99.2.224 · Cited by 742
Cholesterol Reduction in Cardiovascular Disease — Clinical Benefits and Possible Mechanisms
Levine, G. N., Keaney, J. F., & Vita, J. A. (1995) · New England Journal of Medicine · doi:10.1056/nejm199502233320807 · Cited by 673
Homocyst(e)ine Decreases Bioavailable Nitric Oxide by a Mechanism Involving Glutathione Peroxidase
Upchurch, G. R., Welch, G. N., Fabian, A. J., Freedman, J. E., Johnson, J. L., Keaney, J. F., & Loscalzo, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.27.17012 · Cited by 668
Self-citation
Cited by
Sorted by citations
Ighodaro, O. M., & Akinloye, O. A. (2017) · Alexandria Journal of Medicine · doi:10.1016/j.ajme.2017.09.001 · Cited by 4,036
Role of Oxidative Modifications in Atherosclerosis
Stocker, R., & Keaney, J. F. (2004) · Physiological Reviews · doi:10.1152/physrev.00047.2003 · Cited by 2,651
Incalza, M. A., D’Oria, R., Natalicchio, A., Perrini, S., Laviola, L., & Giorgino, F. (2017) · Vascular Pharmacology · doi:10.1016/j.vph.2017.05.005 · Cited by 1,419
Lubos, E., Loscalzo, J., & Handy, D. E. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3586 · Cited by 1,280
Self-citationRedox regulation of mitochondrial function
Handy, D. E., & Loscalzo, J. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4123 · Cited by 588
Self-citation
Metadata
- Authors
- Forgione, M. A., Weiss, N., Heydrick, S., Cap, A., Klings, E. S., Bierl, C., Eberhardt, R. T., Farber, H. W., & Loscalzo, J.
- Affiliations
- Evans Department of Medicine,
- Whitaker Cardiovascular Institute, Department of Pharmacology, and
- Boston University (US)
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2002-04-01
- Volume
- 282
- Issue
- 4
- Pages
- H1255-H1261
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2139527140
- Cited by
- 199
- References
- 41
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 3 · 2023: 8 · 2022: 7 · 2021: 11 · 2020: 5 · 2019: 10 · 2018: 3 · 2017: 9 · 2016: 10 · 2015: 6 · 2014: 9 · 2013: 9 · 2012: 10
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL61795, HL 55993, HL-07224-24, HL58976, R01HL058976, T32HL007224, P50HL055993)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Keywords
- glutathione peroxidase 1, endothelial dysfunction, mesenteric arterioles, endothelium-dependent vasodilation, nitric oxide bioavailability, nitrotyrosine, L-2-oxothiazolidine-4-carboxylic acid, bradykinin, aorta
- MeSH terms
- Animals, Bradykinin, Endothelium, Vascular, Glutathione Peroxidase, Cyclic GMP, Microcirculation, Nitroprusside, Splanchnic Circulation, Methacholine Chloride, Mice, Knockout, Oxidative Stress, Nitric Oxide Synthase, Models, Animal, Mice, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
