Thromboxane A2 potentiates thrombin-induced proliferation of coronary artery smooth muscle cells.
The activation of thrombin is the key event in clot formation after vascular injury. Thrombin itself, but also other clot-derived factors, such as thromboxane A2 (TXA2), are mitogenic for vascular smooth muscle cells. We have studied the possible interactions between thrombin and TXA2 in stimulation of coronary artery smooth muscle cell (SMC) proliferation. Thrombin (1 U/ml) caused a significant proliferatory response in SMC. U 46619, a stable TXA2 mimetic, had only a minor stimulating effect by its own but markedly potentiated the thrombin-induced mitogenesis. A possible mechanism for these potentiating effects is provided by the demonstration of a marked (6 fold) but transient (maximum after 20 min) increase in the expression of TXA2 receptor (TP receptor) mRNA in SMC by thrombin. Since a significant clot-related TXA2 generation was detected for at least 2 hours, the up-regulation of TP receptors by thrombin may represent a mechanism that is relevant for the in vivo situation of SMC proliferation after vessel injury.
Zucker
T P
TP
Institute für Klinische Anaesthesiologie, Heinrich-Heine-Universität Düsseldorf, Germany.
Bönisch
D
D
Muck
S
S
Weber
A A
AA
Bretschneider
E
E
Glusa
E
E
Schrör
K
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000502:physiology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D017482:Receptors, Thromboxane / Q000096:biosynthesis*; D013917:Thrombin / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors; D015854:Up-Regulation
D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D013917:Thrombin