Thrombin-Induced Mitogenesis in Coronary Artery Smooth Muscle Cells Is Potentiated by Thromboxane A 2 and Involves Upregulation of Thromboxane Receptor mRNA

Publisher Website
Google Scholar
Abstract
Background —Previous studies have shown that thrombin is a potent though slow-acting mitogen for vascular smooth muscle cells (SMC). Because thrombin generation in vivo is accompanied by platelet activation, it has been suggested that platelet-derived factors might enhance thrombin-induced SMC proliferation. No information is available so far on the possible role of thromboxane A 2 . Methods and Results —Thrombin (1 U/mL) caused a threefold to fourfold increase of DNA synthesis in cultured bovine coronary artery SMC as assessed from [ 3 H]thymidine incorporation. U 46619, a stable thromboxane A 2 mimetic, had only a minor stimulating effect on its own but potentiated the thrombin effect sixfold to sevenfold above control ( P <.05). These findings were paralleled by a 52±5% ( P <.05) increase in cell number at 48 hours after addition of both mitogens as compared with 24±5% with thrombin alone and no change with U 46619 alone. Thromboxane A 2 receptor mRNA was found to be upregulated sixfold 20 minutes after thrombin stimulation. Pretreatment of SMC with thrombin for 4 hours markedly increased U 46619–induced mitogen-activated protein kinase activity, indicating thrombin-induced upregulation of functional thromboxane receptors in SMC. Conclusions —Thrombin-induced proliferation of SMC is markedly enhanced by thromboxane A 2 . This might result in an enhancement of SMC proliferation by platelet-derived thromboxane A 2 in vivo.

This publication has 31 references indexed in Scilit: