Effect of cyclosporine during initiation of transplant arteriosclerosis. An ultrastructural study in the aorta-transplanted rabbit.
The immunosuppressant cyclosporine protects against the development of experimental transplant arteriosclerosis. To investigate the mechanism underlying this effect, aorta-allografted rabbits were randomly assigned to cyclosporine (n = 6) in the human therapeutic range or to its vehicle (n = 5). Perfusion fixation was performed 2 weeks after the transplantation, followed by light, scanning and transmission electron microscopy examination. Intimal proliferation was absent in native aortas, present in all grafts from vehicle-treated animals, and either absent or sparse in grafts from cyclosporine-treated rabbits. The endothelium of native aortas from both vehicle- and cyclosporine-treated rabbits was normal. Aortic allografts from cyclosporine-treated rabbits exhibited a normal endothelium with only a few adhering mononuclear cells, whereas aortic allografts from vehicle-treated rabbits exhibited an endothelial surface ranging from near-normal with only few adhering platelets and mononuclear cells, to an almost destroyed endothelium, lined with lymphocyte-like cells, monocytes/macrophages, platelets, erythrocytes and fibrin; in the subendothelial layer, mononuclear cells and smooth muscle cells were abundant. These results suggest that damage to the endothelial cells as well as invasion of lymphocytes, monocytes/macrophages and smooth muscle cells into the subendothelial space are important events during initiation of transplant arteriosclerosis, and that cyclosporine largely attenuates these early pathological changes.
Andersen
H O
HO
Department of Thoracic Surgery RT, Rigshospitalet, University of Copenhagen, Denmark.
Qvortrup
K
K
Rostgaard
J
J
Nordestgaard
B G
BG
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000648:ultrastructure; D001013:Aorta, Thoracic / Q000187:drug effects / Q000637:transplantation*; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004727:Endothelium / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D006084:Graft Rejection / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008853:Microscopy; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D014677:Pharmaceutical Vehicles / Q000627:therapeutic use; D011817:Rabbits; D014184:Transplantation, Homologous / Q000276:immunology
D007166:Immunosuppressive Agents; D014677:Pharmaceutical Vehicles; D016572:Cyclosporine; D002784:Cholesterol