Cyclosporin suppresses transplant arteriosclerosis in the aorta-allografted, cholesterol-clamped rabbit. Suppression preceded by decrease in arterial lipoprotein permeability.
The immunosuppressant cyclosporin has been suggested to aggravate as well as retard the development of transplant arteriosclerosis, the major long-term problem for patients with heart transplants. We examined the effect of human therapeutic levels of blood cyclosporin on the development of experimental transplant arteriosclerosis. The thoracic aorta from one rabbit was transplanted as an end-to-side bypass on the abdominal aorta of another rabbit, and plasma cholesterol was clamped at 5 to 7 mmol/L. Cyclosporin markedly suppressed the severity of transplant arteriosclerosis, judged both biochemically and histologically: cholesterol content in aortic transplants was reduced by 70% and 80% after 10 days and 20 days of cholesterol feeding, respectively (both comparisons, P < .01), and after 20 days of cholesterol feeding myointimal proliferation was totally inhibited in grafts from cyclosporin-treated animals, judged from maximal intimal thickness and intimal area on cross sections of grafts (both comparisons, P < .05). In another group of non-cholesterol-fed, aorta-transplanted rabbits, cyclosporin reduced by 90% (P < .01) an otherwise markedly increased permeability to low-density lipoprotein in transplanted aortas. These results suggest that cyclosporin causes a substantial decrease in the severity of transplant arteriosclerosis and that this effect is mediated at least partly via a large decrease in aortic lipoprotein permeability.
Andersen
H O
HO
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen O, Denmark.
Madsen
G
G
Nordestgaard
B G
BG
Hansen
B F
BF
Kjeldsen
K
K
Stender
S
S
D000818:Animals; D001012:Aorta, Abdominal; D001013:Aorta, Thoracic / Q000737:chemistry / Q000166:cytology / Q000637:transplantation*; D001161:Arteriosclerosis / Q000517:prevention & control*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002784:Cholesterol / Q000097:blood*; D016572:Cyclosporine / Q000627:therapeutic use*; D016027:Heart Transplantation / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008074:Lipoproteins / Q000493:pharmacokinetics; D008297:Male; D011817:Rabbits; D016042:Transplantation, Heterotopic
D007166:Immunosuppressive Agents; D008074:Lipoproteins; D016572:Cyclosporine; D002784:Cholesterol