Effect of cyclosporine during initiation of transplant arteriosclerosis. An ultrastructural study in the aorta-transplanted rabbit

• Published in: Atherosclerosis Vol. 133; no. 2; pp. 171 - 181
• Main Authors: Andersen, Henrik Ørbæk, Qvortrup, Klaus, Rostgaard, Jørgen, Nordestgaard, Børge G
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01-09-1997; Elsevier
• Subjects: Animals; Aorta, Abdominal - drug effects; Aorta, Abdominal - ultrastructure; Aorta, Thoracic - drug effects; Aorta, Thoracic - transplantation; Aorta-allografted rabbit; Arteriosclerosis - etiology; Arteriosclerosis - pathology; Arteriosclerosis - prevention & control; Biological and medical sciences; Body Weight - drug effects; Body Weight - physiology; Cholesterol - blood; Cyclosporine; Cyclosporine - administration & dosage; Cyclosporine - pharmacology; Endothelium - drug effects; Endothelium - pathology; Endothelium - ultrastructure; Graft Rejection - prevention & control; Immunomodulators; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacology; Male; Medical sciences; Microscopy; Microscopy, Electron; Microscopy, Electron, Scanning; Pharmaceutical Vehicles - therapeutic use; Pharmacology. Drug treatments; Rabbits; Scanning transmission microscopy; Transmission electron microscopy; Transplant arteriosclerosis; Transplantation, Homologous - immunology; Scanning transmission microscopy; Transplant arteriosclerosis; Transmission electron microscopy; Aorta-allografted rabbit; Cyclosporine; Homograft; Rabbit; Cardiovascular disease; Lagomorpha; Electron microscopy; Vascular disease; Prevention; Pathology; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Atherosclerosis; Graft; Aorta; Complication; Ciclosporin; Immunosuppressive agent
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(97)00123-8

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.