1. Roles of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE-deficient mice.
- Author
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Kobayashi, Takuya, Tahara, Yoshio, Matsumoto, Mayumi, Iguchi, Masako, Sano, Hideto, Murayama, Toshinori, Arai, Hidenori, Oida, Hiroji, Yurugi-kobayashi, Takami, Yamashita, Jun K., Katagiri, Hiroyuki, Majima, Masataka, Yokode, Masayuki, Kita, Toru, and Narumiya, Shuh
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ATHEROSCLEROSIS , *THROMBOXANES , *PROSTACYCLIN , *LABORATORY mice , *BLOOD platelets , *LEUCOCYTES - Abstract
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-/- 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. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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