angiopeptin (cas 113294-82-9), a Somatostatin Analogue, Inhibits Rat Coronary Artery and Aorta Smooth Muscle Cell Proliferation Induced by the Thromboxane A2 Mimetic U46619

Add time:08/18/2019    Source:sciencedirect.com

Thromboxane A2 (TXA2) is a potent mitogenic agent. Its synthesis is increased in transplant patients during rejection episodes, which is the suspected etiology of accelerated transplant arteriosclerosis. Angiopeptin, a stable analogue of somatostatin, inhibits arterial myointimal thickening in a number of vascular balloon injury models of angioplasty and in vivo models of transplant arteriosclerosis. In this study, we investigated whether TXA2-induced smooth muscle cell proliferation is inhibited by Angiopeptin in vitro. Primary rat coronary and aorta smooth muscle cells were cultured in the presence of U46619, a TXA2 mimetic. Proliferation induced by U46619, as determined by 3H-thymidine incorporation, was abrogated by two specific thromboxane receptor antagonists, SQ 30741 and SQ 29548, indicating that the effect of U46619 on smooth muscle cells is a specific receptor-mediated response. We found Angiopeptin to inhibit proliferation following exposure of both coronary and aorta smooth muscle cells to varying concentrations of U46619 for 3 and 6 days. This study demonstrates that U46619 exerts a specific receptor-mediated response stimulating the rat coronary and aorta smooth muscle cell proliferation. This mitogenic effect is obtained by increasing the G1 to S transition rate. Angiopeptin inhibits thromboxane-induced cell proliferation to the same extent as a thromboxane antagonist. This inhibition is obtained by maintaining the noncycling fraction in that Angiopeptin prevents a progression from G0–G1 to S phase.

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