Angiopeptin: a treatment for accelerated myointimal hyperplasia?
Extensive smooth muscle cell proliferation is the major event leading to the narrowing or occlusion of the lumen of the coronary arteries of patients undergoing heart transplantation or percutaneous transluminal coronary angioplasty. The smooth muscle cell proliferation in transplant atherosclerosis may be initiated by immunologic events, allowing the vascular smooth muscle cells to respond with migration and proliferation to circulating growth factors as well as chemoattractants and growth factors released by inflammatory cells and smooth muscle cells themselves. The somatostatin analog angiopeptin is a cyclic octapeptide that has different binding affinities for different somatostatin receptors compared with the parent compound itself. The antiproliferative effects of angiopeptin have been demonstrated in vitro in several tumor cell lines. In a rabbit model of heterotopic heart transplant-accelerated coronary atherosclerosis, angiopeptin has been shown to attenuate myointimal hyperplasia. Further studies in simpler models of myointimal hyperplasia have shown that angiopeptin will inhibit smooth muscle cell proliferation after vascular injury. Further, angiopeptin inhibits thymidine uptake in vitro in pig coronary arteries. Angiopeptin also exerts its inhibitory effect at a very early stage after injury: an 8-hour delay of treatment abolishes the inhibitory effect of angiopeptin on smooth muscle cell proliferation (intimal hyperplasia). On the basis of the experimental data, clinical studies of the inhibitory effect of angiopeptin on prevention of transplant atherosclerosis in heart transplant patients and prevention of restenosis after coronary artery angioplasty are ongoing, as well as are studies in patients undergoing saphenous vein coronary artery bypass surgery.
Department of Surgery, Georgetown Hospital, Washington, DC 20007.
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Foegh
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D016027:Heart Transplantation; D006965:Hyperplasia / Q000188:drug therapy; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D009842:Oligopeptides / Q000627:therapeutic use*; D010456:Peptides, Cyclic; D011183:Postoperative Complications; D051381:Rats; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D009842:Oligopeptides; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin