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Transforming growth factor-ß1 enhances the antifibrinolytic and prothrombotic state of growing endothelial cells in a cell cycle-specific manner

Volker R. Stoldt^*,,1, Oliver Schnorr^*, Klaus Schulze-Osthoff^, and Rudiger E. Scharf^*,

^* Department of Hemostasis and Transfusion Medicine and

Center for Biological and Medical Research, and

Institute of Molecular Medicine, Heinrich Heine University Medical Center, Düsseldorf, Germany

¹Correspondence: Department of Hemostasis and Transfusion Medicine, Laboratory of Vascular Biology, Heinrich Heine University Medical Center, Bldg. 12.49.00, Rm. 9, Moorenstr. 5, D-40225 Dusseldorf, Germany. E-mail: stoldt{at}uni-duesseldorf.de

ABSTRACT

Cell cycle-dependent modulation of protein expression may influence the balance of antithrombotic and prothrombotic properties of endothelial cells. In the present study, we examined the regulation of prothrombotic and antithrombotic molecules by transforming growth factor–ß1 (TGF-ß1) during distinct phases of the cell cycle in human umbilical vein endothelial cells. In the absence of TGF-ß1, the expression of thrombomodulin, the plasminogen activators u-PA and t-PA, and their inhibitor PAI-1 was significantly increased in the S/G2 compared to the G₁ phase. Treatment of endothelial cells with TGF-ß1, however, resulted in elevated expression of PAI-1 specifically in the S/G2 phase, while t-PA and u-PA increased to the same extent in both the G1 and S/G2 phase. These findings demonstrate that the expression of a subset of hemostatically relevant proteins is regulated during endothelial cell cycle and that TGF-ß1 can differentially modulate cell cycle-controlled protein expression.—Stoldt, V. R., Schnorr, O., Schulze-Osthoff, K., Scharf, R. E. Transforming growth factor-ß1 enhances the antifibrinolytic and prothrombotic state of growing endothelial cells in a cell cycle-specific manner.