Angiopeptin inhibition of myointimal hyperplasia after balloon angioplasty of large arteries in hypercholesterolaemic rabbits.
1. Currently, a wide range of drugs is being evaluated for the ability to prevent the restenosis which frequently accompanies percutaneous transluminal coronary angioplasty. Patients undergoing angioplasty are generally hypercholesterolaemic and therefore the possibility that plasma lipids may compromise the efficacy of anti-restenotic drugs must be assessed. A promising drug in several clinical trials for the prevention of restenosis is angiopeptin, an octapeptide analogue of somatostatin that possesses a highly lipophilic terminal. 2. The effect of angiopeptin on myointimal hyperplasia was studied in a rabbit model of arterial balloon catheter injury where the rabbits were made hypercholesterolaemic by a 0.5% cholesterol diet. The degree of subsequent myointimal thickening was measured by morphometry. 3. Angiopeptin (20 micrograms day-1 kg-1) significantly inhibited myointimal thickening by an average of 47% in the infrarenal aorta and both the common and external iliac arteries in the presence of elevated plasma lipids concentrations. Low dose angiopeptin (2 micrograms day-1 kg-1) significantly inhibited myointimal thickening in the external iliac artery but not in the other two vessels. 4. Angiopeptin treatment (20 micrograms day-1 kg-1) did not significantly modify the plasma cholesterol, very-low-density lipoprotein, intermediate-sized low-density lipoprotein, low-density lipoprotein and high-density lipoprotein concentrations that were elevated by the 0.5% cholesterol diet. 5. We conclude that the inhibitory effect of angiopeptin is largely unaffected by elevated plasma lipid concentrations and that this drug did not modify plasma lipid concentrations in rabbits.
Howell
M H
MH
Department of Surgery, Georgetown University Medical Center, Washington, D.C. 20007.
Adams
M M
MM
Wolfe
M S
MS
Foegh
M L
ML
Ramwell
P W
PW
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001013:Aorta, Thoracic / Q000293:injuries / Q000473:pathology; D001157:Arterial Occlusive Diseases / Q000517:prevention & control; D006937:Hypercholesterolemia / Q000473:pathology*; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D007083:Iliac Artery / Q000293:injuries / Q000473:pathology*; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use*; D010456:Peptides, Cyclic; D011817:Rabbits; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017539:Tunica Intima / Q000293:injuries / Q000473:pathology*
D009842:Oligopeptides; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin