| First Author | Kobayashi T | Year | 2004 |
| Journal | J Clin Invest | Volume | 114 |
| Issue | 6 | Pages | 784-94 |
| PubMed ID | 15372102 | Mgi Jnum | J:92843 |
| Mgi Id | MGI:3054602 | Doi | 10.1172/JCI21446 |
| Citation | Kobayashi T, et al. (2004) Roles of thromboxane A(2) and prostacyclin in the development of atherosclerosis in apoE-deficient mice. J Clin Invest 114(6):784-94 |
| abstractText | Production of thromboxane (TX) A2 and PG I2/prostacyclin (PGI2) is increased in patients with atherosclerosis. However, their roles in atherogenesis have not been critically defined. To examine this issue, we cross-bred atherosclerosis-prone apoE-deficient mice with mice deficient in either the TXA receptor (TP) or the PGI receptor (IP). Although they showed levels of serum cholesterol and triglyceride similar to those of apoE-deficient mice, apoE-/-TP-/- mice exhibited a significant delay in atherogenesis, and apoE-/-IP-/- mice exhibited a significant acceleration in atherogenesis compared with mice deficient in apoE alone. The plaques in apoE-/-IP-/- mice showed partial endothelial disruption and exhibited enhanced expression of ICAM-1 and decreased expression of platelet endothelial cell adhesion molecule 1 (PECAM-1) in the overlying endothelial cells compared with those of apoE-/-TP-/- mice. Platelet activation with thrombin ex vivo revealed higher and lower sensitivity for surface P-selectin expression in platelets of apoE-/-IP-/- and apoE-/-TP-/- mice, respectively, than in those of apoE-/- mice. Intravital microscopy of the common carotid artery revealed a significantly greater number of leukocytes rolling on the vessel walls in apoE-/-IP-/- mice than in either apoE-/-TP-/- or apoE-/- mice. We conclude that TXA2 promotes and PGI2 prevents the initiation and progression of atherogenesis through control of platelet activation and leukocyte-endothelial cell interaction. |
