N-acetylcysteine inhibits thrombosis in a murine model of myeloproliferative neoplasm
| العنوان: | N-acetylcysteine inhibits thrombosis in a murine model of myeloproliferative neoplasm |
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| المؤلفون: | Hew Yeng Lai, Stefan Brooks, Laura F. Mendez Luque, Xinyue Chang, Brianna M. Craver, Angela G. Fleischman, Gajalakshmi Ramanathan, Summer Hoang |
| المصدر: | Blood advances, vol 4, iss 2 |
| بيانات النشر: | American Society of Hematology, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, and promotion of well-being, Context (language use), Pharmacology, Cardiovascular, Acetylcysteine, Mice, 03 medical and health sciences, Rare Diseases, 0302 clinical medicine, Polycythemia vera, Clinical Research, hemic and lymphatic diseases, Complementary and Integrative Health, Antithrombotic, medicine, Animals, Humans, Platelet, Platelet activation, 3.3 Nutrition and chemoprevention, Myeloproliferative neoplasm, Myeloid Neoplasia, Myeloproliferative Disorders, business.industry, Prevention, food and beverages, Thrombosis, Hematology, Neutrophil extracellular traps, Prevention of disease and conditions, medicine.disease, 030104 developmental biology, 5.1 Pharmaceuticals, 030220 oncology & carcinogenesis, Development of treatments and therapeutic interventions, business, medicine.drug |
| الوصف: | Thrombosis is a major cause of mortality in patients with myeloproliferative neoplasms (MPNs), though there is currently little to offer patients with MPN beyond aspirin and cytoreductive therapies such as hydroxyurea for primary prevention. Thrombogenesis in MPN involves multiple cellular mechanisms, including platelet activation and neutrophil-extracellular trap formation; therefore, an antithrombotic agent that targets one or more of these processes would be of therapeutic benefit in MPN. Here, we treated the JAK2V617F knockin mouse model of polycythemia vera with N-acetylcysteine (NAC), a sulfhydryl-containing compound with broad effects on glutathione replenishment, free radical scavenging, and reducing disulfide bonds, to investigate its antithrombotic effects in the context of MPN. Strikingly, NAC treatment extended the lifespan of JAK2V617F mice without impacting blood counts or splenomegaly. Using an acute pulmonary thrombosis model in vivo, we found that NAC reduced thrombus formation to a similar extent as the irreversible platelet inhibitor aspirin. In vitro analysis of platelet activation revealed that NAC reduced thrombin-induced platelet-leukocyte aggregate formation in JAK2V617F mice. Furthermore, NAC reduced neutrophil extracellular trap formation in primary human neutrophils from patients with MPN as well as healthy controls. These results provide evidence that N-acetylcysteine inhibits thrombosis in JAK2V617F mice and provide a pre-clinical rationale for investigating NAC as a therapeutic to reduce thrombotic risk in MPN. |
| وصف الملف: | application/pdf |
| تدمد: | 2473-9537 2473-9529 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::df96a2c9862266059919856dccd4c9c0 https://doi.org/10.1182/bloodadvances.2019000967 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....df96a2c9862266059919856dccd4c9c0 |
| قاعدة البيانات: | OpenAIRE |
Full Text via ClinicalKey | تدمد: | 24739537 24739529 |
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