Angiopeptin, a somatostatin analogue, inhibits rat coronary artery and aorta smooth muscle cell proliferation induced by the thromboxane A2 mimetic U46619.
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.
Zhao
Y
Y
Department of Surgery, Georgetown University Medical Center, Washington, DC 20007, USA.
Foegh
M L
ML
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology; D001158:Arteries / Q000166:cytology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000502:physiology; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D002317:Cardiovascular Agents; D009842:Oligopeptides; D010456:Peptides, Cyclic; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; C060347:lanreotide; D013004:Somatostatin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid