Academic Journal
Glutathione Peroxidase-3 Deficiency Promotes Platelet-Dependent Thrombosis In Vivo
| العنوان: | Glutathione Peroxidase-3 Deficiency Promotes Platelet-Dependent Thrombosis In Vivo |
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| المؤلفون: | Jin, Richard C., Mahoney, Christopher E., (Coleman) Anderson, Laura, Ottaviano, Filomena, Croce, Kevin, Leopold, Jane A., Zhang, Ying-Yi, Tang, Shiow-Shih, Handy, Diane E., Loscalzo, Joseph |
| المصدر: | Circulation ; volume 123, issue 18, page 1963-1973 ; ISSN 0009-7322 1524-4539 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health) |
| سنة النشر: | 2011 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1161/circulationaha.110.000034 |
| DOI: | 10.1161/CIRCULATIONAHA.110.000034 |
| الاتاحة: | http://dx.doi.org/10.1161/circulationaha.110.000034 https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.110.000034 |
| رقم الانضمام: | edsbas.19352404 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1161/circulationaha.110.000034 |
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