| First Author | Jin H | Year | 2015 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 35 |
| Issue | 4 | Pages | 838-44 |
| PubMed ID | 25675995 | Mgi Jnum | J:241339 |
| Mgi Id | MGI:5901816 | Doi | 10.1161/ATVBAHA.115.305378 |
| Citation | Jin H, et al. (2015) Endothelial PPAR-gamma protects against vascular thrombosis by downregulating P-selectin expression. Arterioscler Thromb Vasc Biol 35(4):838-44 |
| abstractText | OBJECTIVE: We tested the hypothesis that endothelial peroxisome proliferator-activated receptor-gamma protects against vascular thrombosis using a transgenic mouse model expressing a peroxisome proliferator-activated receptor-gamma 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-kappaB 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. CONCLUSIONS: Endothelial peroxisome proliferator-activated receptor-gamma protects against thrombosis through a mechanism that involves downregulation of P-selectin expression and diminished P-selectin-mediated leukocyte-endothelial interactions. |
