Accelerated cholesterol accumulation in homologous arterial transplants in cholesterol-fed rabbits. A surgical model to study transplantation atherosclerosis.

Abstract

Accelerated coronary artery disease has become a major complication to heart transplantation in humans. Therefore, we have developed a surgical model in the rabbit, with transplantation of the thoracic aorta as a bypass graft onto the abdominal aorta of another rabbit. The model permits the study of cholesterol metabolism in transplanted arteries. The graft did not accumulate cholesterol for as long as 298 days, provided that the rabbits were normocholesterolemic, i.e., with plasma cholesterol levels of 0.3-0.7 mmol/l. However, after a few weeks of cholesterol feeding resulting in plasma cholesterol levels of 2-5 mmol/l, the homologous graft accumulated cholesterol compared with intact aortic tissue in the rabbits and also compared with autologous aortic grafts. The intimal clearance of plasma cholesteryl ester, mainly high density lipoprotein cholesteryl ester, in the luminal layer of the aortic graft was 60-150 nl x cm-2 x hr-1 1-2 hours after transplantation. The intimal clearance in the corresponding intact thoracic aorta of the recipient animal was 5-20 nl x cm-2 x hr-1. The values were 1,500-3,000 nl x cm-2 x hr-1 51-298 days after transplantation, while the intimal clearance of the rabbit's own aorta remained unchanged. A pronounced increase in plasma lipoprotein permeability is thus an early event in transplanted arteries. It results in a higher cholesteryl ester influx that leads to cholesterol accumulation in the artery, but only if the rabbits are fed a cholesterol-enriched diet. This rabbit model may be useful in the search for interventional measures to prevent or diminish the accelerated coronary artery disease in transplanted hearts in humans.