Inhibition of coronary artery transplant atherosclerosis in rabbits with angiopeptin, an octapeptide.

Accelerated coronary atherosclerosis of cardiac allograft occurs in 30-40% of cardiac transplant patients and remains an unsolved clinical problem. The etiology is unknown and anti-platelet drugs are used without conspicuous success. The inhibitory effect of the octapeptide, angiopeptin on coronary atherosclerosis was studied in a previously described rabbit heterotopic cardiac transplant model where allograft rejection is prevented by daily administration of cyclosporin A (CsA, 10 mg/kg per day s.c.). Twenty male New Zealand white rabbits (2.6-2.8 kg) received a heterotopic cardiac transplant from rabbits of the same strain. Donors and recipients were fed a 0.5% cholesterol diet 1 week prior to transplantation which was continued for the recipient until death 6 weeks later. The control group (n = 16) received CsA and saline injections twice daily and the treatment group (n = 4) received CsA and angiopeptin (60 micrograms/rabbit daily s.c.) in 2 divided doses. The treatment began after completion of the transplantation. Coronary artery transplant atherosclerosis was uniformly distributed (tubular) in the entire length of the coronary arteries. Angiopeptin inhibited the intimal hyperplasia in the transplanted heart from 47.5 +/- 2.4% (mean +/- SE) to 25.0 +/- 6.9% and in the native heart from 24.2 +/- 1.4% to 15.7 +/- 1.5%. The intimal hyperplasia is expressed as area of intimal hyperplasia/total vessel area x 100%. A similar inhibition by angiopeptin was seen in lipid deposition in the donor ascending aorta which is transplanted with the heart. Angiopeptin attenuated significantly the hyperplasia and the lipid deposition of the native coronary arteries and aorta but to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS)