Effect of 15-deoxyspergualin on allograft arterio-sclerosis and growth factor synthesis in the rat.
Chronic rejection is a major cause for late graft loss. Typical vascular changes in the grafts are adventitial inflammation, disappearance of myocytes in the media and thickening of the intimal layer. We investigated the effect of a new immunosuppressive drug, 15-deoxyspergualin (DSG), on chronic rejection using our rat aortic allograft model. At the dose of 1.0 mg/kg per day, DSG significantly reduced all histopathological parameters of chronic rejection, thus, inhibiting the generation of allograft arteriosclerosis. Growth factor synthesis in the grafts was determined by reverse transcription reaction with oligo dT primers and semiquantitated by polymerase chain reaction. The expression of several growth factors, PDGF-BB, IGF-1, EGF an TGF-beta, was suppressed to 16-60% of the non-treated allograft level. This indicated that DSG may work via suppression of growth factor synthesis and, thus, inhibits the generation of chronic rejection.
Transplantation Laboratory, University of Helsinki, Finland.
A
A
Räisänen-Sokolowski
P
P
Aho
G
G
Tufveson
P
P
Häyry
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology / Q000637:transplantation*; D001161:Arteriosclerosis / Q000473:pathology*; D000077214:Becaplermin; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006084:Graft Rejection / Q000473:pathology* / Q000517:prevention & control; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics*; D006146:Guanidines / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009336:Necrosis; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011920:Rats, Inbred WF; D014158:Transcription, Genetic / Q000187:drug effects; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology*; D017540:Tunica Media / Q000473:pathology / Q000637:transplantation
D006133:Growth Substances; D006146:Guanidines; D007166:Immunosuppressive Agents; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; C037258:gusperimus