TY - JOUR
AU - Nicholson, M L
AB - Abstract Background Allograft vasculopathy remains the leading cause of late allograft failure following transplantation and can be inhibited by the antiproliferative drug rapamycin. This study assessed the efficacy of combining rapamycin therapy with calcineurin inhibition. Methods Male Sprague–Dawley rats received rapamycin 0·05 mg/kg daily and either tacrolimus 0·1 mg/kg or cyclosporin 5 mg/kg daily, and findings were compared with those in an untreated control group. Animals underwent left common carotid artery balloon angioplasty; the artery was explanted after 2 weeks. Morphometric analysis was performed on transverse sections and the intima: media ratio was calculated. Profibrotic gene expression was measured with competitive reverse transcriptase–polymerase chain reaction at 14 and 28 days. Proliferation was determined with proliferating cell nuclear antigen at 14 and 28 days. Extracellular matrix deposition was quantified with Sirius red. Results The combination of rapamycin and tacrolimus was associated with the greatest reduction in intimal thickening. Furthermore, treatment with rapamycin and tacrolimus significantly attenuated extracellular matrix deposition compared with rapamycin and cyclosporin (P < 0·02). Conclusion The effects of rapamycin in combination with tacrolimus were better than those observed with rapamycin and cyclosporin. References 1 Miller LW . Allograft vascular disease: a disease not limited to hearts . J Heart Lung Transplant 1992 ; 11 : S32 – 7 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 2 Nissen SE , Yock P. Intravascular ultrasound: novel pathophysiological insights and current clinical applications . Circulation 2001 ; 103 : 604 – 16 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Billingham ME . Histopathology of graft coronary disease . J Heart Lung Transplant 1992 ; 3 : S38 – 44 . Google Scholar OpenURL Placeholder Text WorldCat 4 Weis M , von Scheidt W. 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TI - Effects of the combination of rapamycin with tacrolimus or cyclosporin on experimental intimal hyperplasia
JO - British Journal of Surgery
DO - 10.1046/j.1365-2168.2002.02271.x
DA - 2002-12-02
UR - https://www.deepdyve.com/lp/oxford-university-press/effects-of-the-combination-of-rapamycin-with-tacrolimus-or-cyclosporin-hMpgYyIvIs
SP - 1390
EP - 1395
VL - 89
IS - 11
DP - DeepDyve
ER -