Effects of Immunosuppressants on Platelet-Derived Growth Factor-A Chain mRNA Expression and Coronary Arteriosclerosis in Rat Cardiac Allografts

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概要

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• Graft coronary arteriosclerosis (GCA) that results in proliferative and obstructive lesions limits the long-term success of cardiac transplantation. Despite extensive study, the pathogenic mechanisms underlying GCA are still unclear and therapeutic strategies for this condition have been inadequate. In this study, we compared the thera-peutic effectiveness of cyclosporine A (CsA), 15-deoxyspergualin (DSG), and Multiglycosidorum tripterygii (MT) on GCA. In addition, we studied the correlation between the extent of GCA and the degree of platelet-derived growth facter (PDGF)-A chain mRNA expression in cardiac grafts/ Lewis rats receiving heterotropic heart transplants from Wistar King donors were treated with 10mgkg^<-1> day<-1> of CsA (n=7), 5 mgkg^<-1> day<-1> of DSG(n=7) or 30 mgkg^<-1> day^<-1> of MT(n=7) respectively. Histological evaluation of coronary arteriosclerosis and Northern blot analysis of cardiac allograft PDGF-A chain mRNA expression were conducted on day 60 after transplantation. Varying levels of GCA were observed in the 21 transplanted hearts. Significant differences in both the degree of PDGF-A mRNA expression and the extent of GCA were found among the 3 groups. GCA was significantly reduced in allografts treated with MT or DSG in comparison with the level seen in CsA-treated grafts. A significant correlation was found between PDGF-A chain mRNA expression and the grade of arterial intimal thickening (r=0.76, p<0.05) as well as with the incidence of diseased vessels (r=0.82, p<0.01). Our results indicate that both MT and DSG are more effective in the treatment of GCA than CsA. In our cardiac allografts, the degree of PDGF-A chain mRNA expression correlated well with the extent of GCA, suggesting that PDGF-A may play an important role in the development of transplant-related GCA.

• 社団法人日本循環器学会の論文
• 1999-03-20

著者

• Koyanagi Hitoshi

  Department Of Cardiovascular Surgery The National Cardiovascular Center

• HACHIDA Mitsuhiro

  Department of Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women's Medical University

• Koyanagi Hitoshi

  The Department Of Cardiovascular Surgery The Heart Institute Of Japan Tokyo Women's Medical Uni

• Koyanagi Hitoshi

  The Department Of Cardiovascular Surgery The Heart Institute Of Japan Tokyo Women's Medical Col

• Zhang Xi-long

  Department of Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women's Medical College

• Lu Hua

  Department of Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women's Medical College

• Hoshi Hironobu

  Department of Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women's Medical College

• Koyanagi Hitoshi

  Department Of Cardiology Musashino Red Cross Hospital

• Hachida Mitsuhiro

  The Department Of Cardiovascular Surgery The Heart Institute Of Japan Tokyo Women's Medical Uni

• Hachida Mitsuhiro

  Department Of Cardiovascular Surgery The Heart Institute Of Japan Tokyo Women's Medical Univers

• Lu Hua

  Department Of Cardiovascular Surgery The Heart Institute Of Japan Tokyo Women's Medical College

• Zhang Xi-long

  Department Of Cardiovascular Surgery The Heart Institute Of Japan Tokyo Women's Medical College

• Hoshi Hironobu

  The Department Of Cardiovascular Surgery The Heart Institute Of Japan Tokyo Women's Medical Uni

• Kasanuki Hiroshi

  The Heart Institute Of Japan

• Hirosawa Koshichira

  Department Of Cardiovascular Surgery The Heart Institute Of Japan Tokyo Women's Medical Univers

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