Roles of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE-deficient mice

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

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Abstract

Production of thromboxane (TX) A2 and PGI2/ 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.

Original languageEnglish
Pages (from-to)784-794
Number of pages11
JournalJournal of Clinical Investigation
Volume114
Issue number6
DOIs
Publication statusPublished - 2004 Sep
Externally publishedYes

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Thromboxane A2
Apolipoproteins E
Epoprostenol
Atherosclerosis
Platelet Activation
Endothelial Cells
Leukocyte Rolling
Thromboxane Receptors
CD31 Antigens
P-Selectin
Common Carotid Artery
Intercellular Adhesion Molecule-1
Thrombin
Cell Communication
Triglycerides
Leukocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kobayashi, T., Tahara, Y., Matsumoto, M., Iguchi, M., Sano, H., Murayama, T., ... Narumiya, S. (2004). Roles of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE-deficient mice. Journal of Clinical Investigation, 114(6), 784-794. https://doi.org/10.1172/JCI200421446

Roles of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE-deficient mice. / 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; Narumiya, Shuh.

In: Journal of Clinical Investigation, Vol. 114, No. 6, 09.2004, p. 784-794.

Research output: Contribution to journalArticle

Kobayashi, T, Tahara, Y, Matsumoto, M, Iguchi, M, Sano, H, Murayama, T, Arai, H, Oida, H, Yurugi-Kobayashi, T, Yamashita, JK, Katagiri, H, Majima, M, Yokode, M, Kita, T & Narumiya, S 2004, 'Roles of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE-deficient mice', Journal of Clinical Investigation, vol. 114, no. 6, pp. 784-794. https://doi.org/10.1172/JCI200421446
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 ; Narumiya, Shuh. / Roles of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE-deficient mice. In: Journal of Clinical Investigation. 2004 ; Vol. 114, No. 6. pp. 784-794.
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