How @entity205 modifies histological and molecular events in the vascular wall during chronic rejection of XXXX cardiac allografts.

@entity1 @entity1667 @entity297 @entity500 @entity870 @entity1294 @entity205 @entity299 @entity35 @entity4288 @entity1590
Accelerated allograft @entity4288 (chronic rejection) has emerged as a major factor affecting long-term survival of @entity1 cardiac allografts. The underlying mechanism of this disorder remains unclear. The purpose of this study was to investigate the effect of @entity205 on the development of @entity299 at the cellular and molecular level. Heterotopic @entity35 cardiac allografts from DA donors to WF recipients, with a strong genetic disparity in major histocompatibility complex and non-major histocompatibility complex loci, were used. The allograft recipients received triple-drug immunosuppression consisting of @entity1667 (0.5 mg/kg/day), @entity500 (2 mg/kg/day), and three different doses of @entity205 ( @entity870 ; 5, 10, and 20 mg/kg/day). The grafts were removed 3 months after transplantation and processed for histology and immunohistochemistry. Low dose @entity870 (5 mg/kg/day) was associated with a severe form of intimal cell accumulation and intimal thickening in epicardial arteries and in smaller intramyocardial arterioles with nearly occluded vessel lumens 3 months after transplantation. The intermediate dose @entity870 (10 mg/kg/day) significantly inhibited arterial intimal thickening but was not efficient in reducing intimal cell accumulation. Instead, high dose @entity870 (20 mg/kg/day) significantly inhibited all arteriosclerotic vascular wall changes in the allografts. Immunohistochemistry revealed that the occluded epicardial arteries of cardiac allografts with low dose @entity870 expressed @entity297 on the endothelium. Higher @entity870 doses significantly reduced the expression of endothelial @entity297 . Neither @entity1590 nor major histocompatibility complex class II were expressed. Perivascular arterial infiltrates consisting of T helper cells and monocytes/macrophages were a characteristic finding in the allograft with low dose @entity870 . In the allografts treated with higher doses of @entity870 , arterial perivascular infiltrates were seldom seen. Our results conclusively demonstrate that sufficient immunosuppression with @entity870 inhibits intimal thickening and intimal cell accumulation of long-surviving @entity35 cardiac allografts in a dose-dependent fashion. @entity1294 alterations associated with increased expression of arterial endothelial @entity297 were totally down-regulated by high doses of @entity870 .
