Endothelial PPAR-γ Protects Against Vascular Thrombosis by Downregulating P-Selectin Expression
| العنوان: | Endothelial PPAR-γ Protects Against Vascular Thrombosis by Downregulating P-Selectin Expression |
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| المؤلفون: | Curt D. Sigmund, Anil K. Chauhan, Pimonrat Ketsawatsomkron, Ilya O. Blokhin, Steven R. Lentz, Hong Jin, Milena A. Gebska, Henry L. Keen, Katina M. Wilson |
| المصدر: | Arteriosclerosis, Thrombosis, and Vascular Biology. 35:838-844 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Carotid Artery Diseases, Male, Genetically modified mouse, medicine.medical_specialty, Time Factors, Endothelium, P-selectin, Carotid Artery, Common, Neutrophils, Down-Regulation, Peroxisome proliferator-activated receptor, Mice, Transgenic, Vena Cava, Inferior, Biology, Article, Antibodies, Downregulation and upregulation, Internal medicine, medicine, Animals, Humans, Leukocyte Rolling, RNA, Messenger, Receptor, Venous Thrombosis, chemistry.chemical_classification, Endothelial Cells, Thrombosis, medicine.disease, Mice, Inbred C57BL, PPAR gamma, Disease Models, Animal, P-Selectin, Venous thrombosis, medicine.anatomical_structure, Endocrinology, chemistry, Mutation, Immunology, Cardiology and Cardiovascular Medicine |
| الوصف: | Objective— We tested the hypothesis that endothelial peroxisome proliferator–activated receptor-γ protects against vascular thrombosis using a transgenic mouse model expressing a peroxisome proliferator–activated receptor-γ mutant (E-V290M) selectively in endothelium. Approach and Results— The time to occlusive thrombosis of the carotid artery was significantly shortened in E-V290M mice compared with nontransgenic littermates after either chemical injury with ferric chloride (5.1±0.2 versus 10.1±3.3 minutes; P =0.01) or photochemical injury with rose bengal (48±9 versus 74±9 minutes; P =0.04). Gene set enrichment analysis demonstrated the upregulation of NF-κB target genes, including P-selectin, in aortic endothelial cells from E-V290M mice ( P P P =0.02). The shortened time to arterial occlusion in E-V290M mice was reversed by administration of P-selectin–blocking antibodies or neutrophil-depleting antibodies ( P =0.04 and P =0.02, respectively) before photochemical injury. Conclusions— Endothelial peroxisome proliferator–activated receptor-γ protects against thrombosis through a mechanism that involves downregulation of P-selectin expression and diminished P-selectin–mediated leukocyte–endothelial interactions. |
| تدمد: | 1524-4636 1079-5642 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b614353f85a78b76ea36973ee90c0c59 https://doi.org/10.1161/atvbaha.115.305378 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b614353f85a78b76ea36973ee90c0c59 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244636 10795642 |
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