Serotonin induces the expression of tissue factor and plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells by Hidehiko Kawano, Hajime.

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Presentation transcript:

Serotonin induces the expression of tissue factor and plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells by 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 Blood Volume 97(6):1697-1702 March 15, 2001 ©2001 by American Society of Hematology

Effects of 5-HT on TF and TFPI mRNA expression Effects of 5-HT on TF and TFPI mRNA expression.(A) Dose-dependent effects of 5-HT. Effects of 5-HT on TF and TFPI mRNA expression.(A) Dose-dependent effects of 5-HT. (B) Time-dependent effects of 5-HT. TF and TFPI mRNA expression was normalized to GAPDH mRNA expression. Relative TF mRNA expression, ▪; TFPI, ■. Each bar represents the mean ± SEM of 3 independent experiments (*P < .05 versus vehicle-treated controls). Relative TF and TFPI mRNA expressions represent the fold increase in normalized TF and TFPI mRNA expression compared to vehicle-treated controls, respectively. Hidehiko Kawano et al. Blood 2001;97:1697-1702 ©2001 by American Society of Hematology

Effects of 5-HT on PAI-1 and TPA mRNA expression Effects of 5-HT on PAI-1 and TPA mRNA expression.(A) Dose-dependent effects of 5-HT. Effects of 5-HT on PAI-1 and TPA mRNA expression.(A) Dose-dependent effects of 5-HT. (B) Time-dependent effects of 5-HT. Graph showing relative PAI-1 (▪) and TPA (■) mRNA expression represents the fold increase in corrected PAI-1 and TPA mRNA expression compared to vehicle-treated controls, respectively. Each bar represents the mean ± SEM of 3 independent experiments (*P < .05 versus vehicle-treated controls). Hidehiko Kawano et al. Blood 2001;97:1697-1702 ©2001 by American Society of Hematology

Effects of 5-HT on the TF activity on the RAEC surface Effects of 5-HT on the TF activity on the RAEC surface.(A) Dose-dependent effects of 5-HT. Effects of 5-HT on the TF activity on the RAEC surface.(A) Dose-dependent effects of 5-HT. Each bar represents the mean ± SEM of 3 independent experiments (*P < .05 versus vehicle-treated controls). (B) Time-dependent effect of 5-HT. ▪, 5-HT, 10 μM; ■, vehicle. Hidehiko Kawano et al. Blood 2001;97:1697-1702 ©2001 by American Society of Hematology

Effects of 5-HT on the concentration of functionally active PAI-1 in the medium.(A) Dose-dependent effects of 5-HT. Effects of 5-HT on the concentration of functionally active PAI-1 in the medium.(A) Dose-dependent effects of 5-HT. Each bar represents the mean ± SEM of 3 independent experiments (*P < .05 versus vehicle-treated controls). (B) Time-dependent effects of 5-HT. ▪, 5-HT, 10 μM; ■, vehicle. Hidehiko Kawano et al. Blood 2001;97:1697-1702 ©2001 by American Society of Hematology

Inhibitory effects of methiothepin (a 5-HT1/5-HT2 receptor antagonist) on 5-HT–induced mRNA expression.(A) TF mRNA expression. Inhibitory effects of methiothepin (a 5-HT1/5-HT2 receptor antagonist) on 5-HT–induced mRNA expression.(A) TF mRNA expression. (B) PAI-1 mRNA expression. Quiescent RAECs were preincubated with the indicated concentrations of methiothepin for 30 minutes and then cultured with serotonin 1 μM for 2 or 3 hours. Relative TF and PAI-1 mRNA expression represent the fold increase in normalized TF and PAI-1 mRNA expression compared to vehicle-treated controls, respectively. Each bar represents the mean ± SEM of 3 independent experiments (*P < .05 versus RAECs treated with 5-HT only). Hidehiko Kawano et al. Blood 2001;97:1697-1702 ©2001 by American Society of Hematology

Inhibitory effects of MCI-9042 (a 5-HT2Areceptor antagonist) on 5-HT–induced mRNA expression.(A) TF mRNA expression. Inhibitory effects of MCI-9042 (a 5-HT2Areceptor antagonist) on 5-HT–induced mRNA expression.(A) TF mRNA expression. (B) PAI-1 mRNA expression. Quiescent RAECs were preincubated with the indicated concentrations of MCI-9042 for 30 minutes and then cultured with serotonin 1 μM for 2 or 3 hours. Relative TF and PAI-1 mRNA expression represent the fold increase in normalized TF and PAI-1 mRNA expression compared to expression in vehicle-treated controls. Each bar represents the mean ± SEM of 3 independent experiments (*P < .05 versus RAECs treated with 5-HT only). Hidehiko Kawano et al. Blood 2001;97:1697-1702 ©2001 by American Society of Hematology