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Blood, 15 March 2001, Vol. 97, No. 6, pp. 1697-1702
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Serotonin induces the expression of tissue factor and plasminogen
activator inhibitor-1 in cultured rat aortic endothelial cells
Hidehiko Kawano,
Hajime Tsuji,
Hiromi Nishimura,
Shinzo Kimura,
Shingo Yano,
Naoki Ukimura,
Yasufumi Kunieda,
Masami Yoshizumi,
Tatsuya Sugano,
Katsumi Nakagawa,
Haruchika Masuda,
Shohei Sawada, and
Masao Nakagawa
From the Second Department of Medicine, Kyoto
Prefectural University of Medicine, Kyoto, Japan.
Serotonin (5-hydroxytryptamine, or 5-HT), released from
activated platelets, not only accelerates aggregation of platelets but
also is known to promote mitosis, migration, and contraction of
vascular smooth muscle cells (VSMCs). These effects are considered to
contribute to thrombus formation and atherosclerosis. The aim of this
study was to investigate the effects of 5-HT on the expressions of
coagulative and fibrinolytic factors in rat aortic endothelial cells.
Endothelial cells were stimulated with various concentrations of 5-HT
(0.1~10 µM), and the expressions of tissue factor (TF), tissue
factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1
(PAI-1), and tissue-type plasminogen activator (TPA) messenger RNAs
(mRNAs) were evaluated by Northern blot analysis. The activities of TF
and PAI-1 were also measured. TF and PAI-1 mRNA were increased
significantly in a concentration- and time-dependent manner. However,
TFPI and TPA mRNA expression did not change. The inductions of TF and
PAI-1 mRNAs were inhibited by a
5-HT1/5-HT2 receptor antagonist
(methiothepin) and a selective 5-HT2A receptor antagonist
(MCI-9042). These results indicate that 5-HT increases procoagulant
activity and reduces fibrinolytic activities of endothelial cells
through the 5-HT2A receptor. It was concluded that the
modulation of procoagulant and hypofibrinolytic activities of
endothelial cells by 5-HT synergistically promotes thrombus formation
at the site of vessel injury with the platelet aggregation, VSMC
contraction, and VSMC proliferation.
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