Roles of Thromboxane A(2) and Prostacyclin in the Development of Atherosclerosis in ApoE-deficient Mice

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2004 Sep 17

PMID 15372102

Citations 127

Authors

Takuya Kobayashi

Yoshio Tahara

Mayumi Matsumoto

Masako Iguchi

Hideto Sano

Toshinori Murayama

Hidenori Arai

Hiroji Oida

Takami Yurugi-Kobayashi

Jun K Yamashita

Hiroyuki Katagiri

Masataka Majima

Masayuki Yokode

Toru Kita

Shuh Narumiya

Affiliations

Soon will be listed here.

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-/-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.

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