Tyrosine kinase inhibitor suppresses coronary arteriosclerotic changes and vasospastic responses induced by chronic treatment with interleukin-1β in pigs in vivo

Akira Ito, Hiroaki Shimokawa, Toshiaki Kadokami, Yoshihiro Fukumoto, M. Koji Owada, Tadayoshi Shiraishi, Ryuichi Nakaike, Tsuneo Takayanagi, Kensuke Egashira, Akira Takeshita

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Abstract

We recently demonstrated that chronic treatment with IL-1β induces coronary arteriosclerotic changes and vasospastic responses to autacoids in pigs in vivo and that those responses are importantly mediated by PDGF. The receptors for PDGF and other major growth factors are known to have tyrosine kinase activity. We therefore investigated the effects of a selective tyrosine kinase inhibitor, ST 638, on those responses induced by IL-1β in our swine model. Intimal thickening and coronary vasospastic responses to serotonin and histamine were induced at the site of the coronary artery where IL-1β was chronically and locally applied. These responses were significantly suppressed in a dose-dependent manner by cotreatment with ST 638. In addition, ST 494, which is an inactive form of ST 638, did not inhibit those responses. The treatment with ST 638 alone did not affect the coronary vasoconstricting responses to the autacoids. Immunoblotting using an antibody to phosphotyrosines confirmed the inhibitory effects of ST 638 on the tyrosine phosphorylations induced by IL-1β. These results thus suggest that tyrosine kinase activation may play an important role in mediating the effects of IL-1β, while also suggesting that ST 638 has an inhibitory effect on the arteriosclerotic changes and vasospastic responses to autacoids in our swine model in vivo.

Original languageEnglish
Pages (from-to)1288-1294
Number of pages7
JournalJournal of Clinical Investigation
Volume96
Issue number3
DOIs
Publication statusPublished - Jan 1 1995

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Interleukin-1
Protein-Tyrosine Kinases
Swine
Autacoids
Tunica Intima
Platelet-Derived Growth Factor Receptors
Phosphotyrosine
Immunoblotting
Histamine
Tyrosine
ST 638
Serotonin
Intercellular Signaling Peptides and Proteins
Coronary Vessels
Phosphorylation
Antibodies

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Tyrosine kinase inhibitor suppresses coronary arteriosclerotic changes and vasospastic responses induced by chronic treatment with interleukin-1β in pigs in vivo. / Ito, Akira; Shimokawa, Hiroaki; Kadokami, Toshiaki; Fukumoto, Yoshihiro; Owada, M. Koji; Shiraishi, Tadayoshi; Nakaike, Ryuichi; Takayanagi, Tsuneo; Egashira, Kensuke; Takeshita, Akira.

In: Journal of Clinical Investigation, Vol. 96, No. 3, 01.01.1995, p. 1288-1294.

Research output: Contribution to journalArticle

Ito, Akira ; Shimokawa, Hiroaki ; Kadokami, Toshiaki ; Fukumoto, Yoshihiro ; Owada, M. Koji ; Shiraishi, Tadayoshi ; Nakaike, Ryuichi ; Takayanagi, Tsuneo ; Egashira, Kensuke ; Takeshita, Akira. / Tyrosine kinase inhibitor suppresses coronary arteriosclerotic changes and vasospastic responses induced by chronic treatment with interleukin-1β in pigs in vivo. In: Journal of Clinical Investigation. 1995 ; Vol. 96, No. 3. pp. 1288-1294.
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