Peptide inhibition of myointimal proliferation by angiopeptin, a somatostatin analogue.
Vascular smooth muscle cell hyperplasia is a major component of atherogenesis in various animal models. Angiopeptin, a cyclic octapeptide analogue of somatostatin, markedly inhibits myointimal proliferation in response to endothelial cell injury in the rat carotid artery, rabbit aorta and iliac arteries and in coronary arteries of transplanted rabbit hearts. Angiopeptin does not affect serum lipid profiles in nonhuman primates. It is unlikely, therefore, that its antiproliferative effect is mediated by alterations in cholesterol metabolism. Angiopeptin and other peptide analogues of somatostatin are potent inhibitors of growth hormone release and insulin-like growth factor-1 production. However, inhibition of smooth muscle cell proliferation in vivo is not a property common to all somatostatin analogues. This suggests that plasma growth hormone and growth hormone-dependent insulin-like growth factor-1 production are not physiologic stimuli for myointimal proliferation in vivo. Angiopeptin inhibits 3H-thymidine incorporation into rat carotid artery explants, suggesting a local effect on autocrine or paracrine mechanisms regulating cell growth. In view of its potent inhibitory effect on smooth muscle cell replication, angiopeptin may have clinical utility in preventing restenosis after percutaneous transluminal coronary angioplasty and in preventing accelerated coronary atherosclerosis after cardiac transplantation.
Lundergan
C F
CF
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, D.C. 20007.
Foegh
M L
ML
Ramwell
P W
PW
D000595:Amino Acid Sequence; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009842:Oligopeptides / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D010456:Peptides, Cyclic; D011817:Rabbits; D051381:Rats; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use
D009842:Oligopeptides; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin