Angiopeptin as a potent inhibitor of myointimal hyperplasia. Systemic injection and local administration via impregnation in a biodegradable polymeric gel.
We studied a pharmacologic approach using a potent peptidyl antiproliferative agent, angiopeptin, to prevent the myointimal hyperplasia that occurs as a diseased vessel is replaced with an artificial graft or treated by an intravascular device. In vitro cell culture studies showed that the proliferative potential of smooth muscle cells was dose dependently reduced, whereas the migratory response was reduced to a lesser degree. In a well defined injured rat artery model, in which a denuded aorta was prepared by collagenase treatment, followed by isotransplantation, a remarkable suppressive effect of angiopeptin on myointimal hyperplasia was observed with daily subcutaneous injection. Local sustained release from a biodegradable polymeric gel coated on an injured vessel was also effective in the prevention of myointimal hyperplasia. Slightly retarded endothelial regeneration was noticed. The potential application to small caliber artificial grafts is discussed.
Matsuda
T
T
Department of Bioengineering, National Cardiovascular Center Research Institute, Osaka, Japan.
Motomura
N
N
Oka
T
T
D000287:Administration, Topical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001013:Aorta, Thoracic / Q000473:pathology / Q000637:transplantation; D001807:Blood Vessel Prosthesis; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D005352:Fibromuscular Dysplasia / Q000473:pathology*; D006083:Graft Occlusion, Vascular / Q000473:pathology*; D007279:Injections, Subcutaneous; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D009842:Oligopeptides / Q000008:administration & dosage*; D010456:Peptides, Cyclic; D051381:Rats; D011917:Rats, Inbred Lew; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D000970:Antineoplastic Agents; D009842:Oligopeptides; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin