Serotonin induces the expression of tissue factor and plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells.
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 approximately 10 microM), 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.
Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. kawano@gemini.kpu-m.ac.jp
H
H
Kawano
H
H
Tsuji
H
H
Nishimura
S
S
Kimura
S
S
Yano
N
N
Ukimura
Y
Y
Kunieda
M
M
Yoshizumi
T
T
Sugano
K
K
Nakagawa
H
H
Masuda
S
S
Sawada
M
M
Nakagawa
D000818:Animals; D001011:Aorta; D001779:Blood Coagulation Factors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D004730:Endothelium, Vascular / Q000166:cytology; D005343:Fibrinolytic Agents / Q000378:metabolism; D006490:Hemostatics / Q000378:metabolism; D008074:Lipoproteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D013925:Thromboplastin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D001779:Blood Coagulation Factors; D005343:Fibrinolytic Agents; D006490:Hemostatics; D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C051928:lipoprotein-associated coagulation inhibitor; D012701:Serotonin; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator