The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Glutathione Peroxidase-3 Deficiency Promotes Platelet-Dependent Thrombosis In Vivo
Open accessAbstract
Background—: Glutathione peroxidase-3 (GPx-3) is a selenocysteine-containing plasma protein that scavenges reactive oxygen species in the extracellular compartment. A deficiency of this enzyme has been associated with platelet-dependent thrombosis, and a promoter haplotype with reduced function has been associated with stroke risk. Methods and Results—: We recently developed a genetic mouse model to assess platelet function and thrombosis in the setting of GPx-3 deficiency. The GPx-3(−/−)mice showed an attenuated bleeding time and an enhanced aggregation response to the agonist ADP compared with wild-type mice. GPx-3(−/−)mice displayed increased plasma levels of soluble P-selectin and decreased plasma cyclic cGMP compared with wild-type mice. ADP infusion-induced platelet aggregation in the pulmonary vasculature produced a more robust platelet activation response in the GPx-3(−/−)than wild-type mice; histological sections from the pulmonary vasculature of GPx-3(−/−)compared with wild-type mice showed increased platelet-rich thrombi and a higher percentage of occluded vessels. Cremaster muscle preparations revealed endothelial dysfunction in the GPx-3(−/−)compared with wild-type mice. With a no-flow ischemia-reperfusion stroke model, GPx-3(−/−)mice had significantly larger cerebral infarctions compared with wild-type mice and platelet-dependent strokes. To assess the neuroprotective role of antioxidants in this model, we found that manganese(III) meso-tetrakis(4-benzoic acid)porphyrin treatment reduced stroke size in GPx-3(−/−)mice compared with vehicle-treated controls. Conclusions—: These findings demonstrate that GPx-3 deficiency results in a prothrombotic state and vascular dysfunction that promotes platelet-dependent arterial thrombosis. These data illustrate the importance of this plasma antioxidant enzyme in regulating platelet activity, endothelial function, platelet-dependent thrombosis, and vascular thrombotic propensity.
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“Deficiency of GPx-3 in humans or knockout mice potentiates platelet activation and thrombosis (139, 193, 212).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [193]
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“Furthermore, in GPx-3 knockout mice, deficiency of this extracellular antioxidant causes endothelial dysfunction and increased sensitivity to neuronal injury in a brain model of ischemia reperfusion injury by mechanisms related to its key functions as an antioxidant enzyme and regulator of platelet-dependent thrombosis (193).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [193]
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NAD(P)H oxidase–dependent platelet superoxide anion release increases platelet recruitment
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Brigelius-Flohé, R., & Maiorino, M. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2012.11.020 · Cited by 1,904
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Brill, A. G., Fuchs, T. A., Savchenko, A. S., Thomas, G. M., Martinod, K., Meyer, S. F. D., Bhandari, A. A., & Wagner, D. D. (2011) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2011.04544.x · Cited by 933
Redox regulation of mitochondrial function
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Zuo, L., Prather, E. R., Stetskiv, M., Garrison, D. E., Meade, J. R., Peace, T. I., & Zhou, T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184472 · Cited by 560
Metadata
- Authors
- Jin, R. C., Mahoney, C. E., (Coleman) Anderson, L., Ottaviano, F., Croce, K., Leopold, J. A., Zhang, Y.-Y., Tang, S.-S., Handy, D. E., & Loscalzo, J.
- Affiliations
- Brigham and Women's Hospital (US)
- From the Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
- ORCID
- Venue
- Circulation
- Published
- 2011-05-10
- Volume
- 123
- Issue
- 18
- Pages
- 1963-1973
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC3107543
- OpenAlex
- W2058584041
- Cited by
- 186
- References
- 33
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 16 · 2023: 13 · 2022: 22 · 2021: 11 · 2020: 7 · 2019: 11 · 2018: 9 · 2017: 8 · 2016: 19 · 2015: 13 · 2014: 11 · 2013: 14 · 2012: 5
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hv28178-12-0-0)
- National Heart, Lung, and Blood Institute (HL 089734, HL081587, HL 070819, K08HL086672, U54HL070819, HL086672, P01HL081587, N01-HV-028178, R21HL089734, R01HL105301, P01HL048743, HL-061795, R37HL061795)
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Keywords
- glutathione peroxidase 3, platelet aggregation, ADP-induced aggregation, soluble P-selectin, pulmonary vasculature, endothelial dysfunction, cerebral infarction, manganese porphyrin, antioxidants, reactive oxygen species, selenocysteine, genetic mouse models
- MeSH terms
- Adenosine Diphosphate, Animals, Antioxidants, Bleeding Time, Blood Platelets, Disease Models, Animal, Endothelium, Vascular, Genotype, Glutathione, Glutathione Peroxidase, Cyclic GMP, Platelet Aggregation, Risk Factors, Thrombosis, Reactive Oxygen Species, Mice, Knockout, P-Selectin, Infarction, Middle Cerebral Artery, Mice
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