Late Cyclosporine Treatment Ameliorates Established Coronary Graft Disease in Rat Allografts

Cyclosporin A Inhibits Apoptosis of Human Endothelial Cells by Preventing Release of Cytochrome C From Mitochondria

“…11 CSA is known to prevent atherosclerosis. 8,9,16 The results of the present study demonstrating an inhibition of endothelial cell apoptosis by CSA might provide a clue to explain the antiatherosclerotic effects of CSA. The concept that CSA treatment suppresses transplant atherosclerosis is supported by the finding that the use of therapeutic levels of cyclosporine in an experimental model of transplant atherosclerosis clearly has a substantial inhibitory effect on the development of transplant atherosclerosis.…”

“…The findings of the present study may give mechanistic insights into CSA action and may support the results of several experimental studies that demonstrate an antiatherosclerotic effect of CSA in transplant atherosclerosis as well as hyperlipidemiainduced atherosclerosis. 8,9,16 In cardiac heart transplants, accelerated coronary atherosclerosis has become the principal cause of late death and allograft dysfunction. 17 Accelerated atherosclerosis is assumed to be mediated by alloimmunity; however, additional "antigen-independent" mechanisms may also account for the development of transplant atherosclerosis.…”

Cyclosporine mitigates graft coronary artery disease in murine cardiac allografts: Description and validation of a novel fully allogeneic model

“…Contradictory data presented by other investigators showed that CsA is effective in preventing and reversing established vascular lesions in a rodent cardiac allograft model. 8,9 Two of our groups of mice showed Ͼ50% survival at 30 days (i.e., the CsA 20/30-day and CsA 30/30-day groups), and GCAD was significantly less frequent in the CsA 30/30-day group in comparison to that in the CsA 20/30-day group. These outcomes suggest a therapeutic effect of CsA on GCAD.…”

“…Several studies have shown that CsA causes magnesium wasting through the kidneys, leading to hypomagnesemia. 8,9 Hypomagnesemia seems to be a reasonable explanation for the unexpected high loss of graft function in the CsA 30/30-day group. However, magnesium levels were not measured in this study.…”

“…Magnesium wasting, 8,9 hypertension 10,11 and nephrotoxicity are described as side effects both experimentally and clinically. 9,12 In clinical practice, the most common problem is nephrotoxicity. All recipient animals in our study had normal blood creatinine concentrations (Ͻ0.6 mg/dl) at 10 and 30 days after transplantation, indicating no nephrotoxicity due to CsA.…”