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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Animals, Antibodies, Carotid Artery Diseases, Carotid Artery, Common, Disease Models, Animal, Down-Regulation, Endothelial Cells, Humans, Leukocyte Rolling, Male, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Neutrophils, P-Selectin, PPAR gamma, RNA, Messenger, Thrombosis, Time Factors, Vena Cava, Inferior, Venous Thrombosis.
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Does endothelial PPAR-γ protect against vascular thrombosis by downregulating P-selectin expression? Context: 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. 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<0.001). Plasma P-selectin and carotid artery P-selectin mRNA were elevated in E-V290M mice (P<0.05). P-selectin-dependent leukocyte rolling on mesenteric venules was increased in E-V290M mice compared with nontransgenic mice (53 ± 8 versus 25 ± 7 per minute; 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.
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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. Final Decision: yes