Histomorphometric comparison of cardiac allograft vasculopathy in miniature swine
| Autor: | David H. Sachs, Margaret L. Schwarze, Christian LeGuern, Stuart L. Houser, Joren C. Madsen, Yasuli Fuchimoto, Isabel M. McMorrow |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Pulmonary and Respiratory Medicine
Graft Rejection Pathology medicine.medical_specialty medicine.medical_treatment Miniature swine Coronary Disease Interferon-gamma medicine Animals Heart transplantation Immunosuppression Therapy Transplantation business.industry Vascular disease Myocardium Histology Immunosuppression medicine.disease Histocompatibility Disease Models Animal Gene Expression Regulation Molecular Probes Immunohistochemistry Heart Transplantation Swine Miniature Surgery Cardiology and Cardiovascular Medicine business |
| Zdroj: | The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 23(1) |
| ISSN: | 1053-2498 |
| Popis: | Background: Whether the pathologic characteristics of vascular lesions manifested in recipients with cardiac allograft vasculopathy (CAV) differ with the severity of the histocompatibility barrier crossed at transplantation or with the type or amount of immunosuppression used to prolong graft survival is unclear. We used miniature swine to determine whether a wide variance in heart transplantation protocols, both in histoincompatibility and immunosuppression, affects the histomorphometry of CAV. Methods: We compared explanted hearts from major histocompatibility complex Class I-disparate recipients who were treated for 12 days with cyclosporine (Group 1) with minor-antigen-disparate hearts transplanted into mixed chimeric recipients previously engrafted with donor hematopoietic progenitor cells (Group 2). We analyzed coronary intimal lesions using computerized morphometry, immunohistochemistry, and TUNEL assay. Myocardial cytokine-gene expression was determined using RNAse protection assays and reverse-transcriptase polymerase chain reaction. Results: The prevalence of CAV in Group 2 was significantly less than that observed in Group 1, but the severity of the lesions in both groups was similar. The vascular lesions that developed in both groups demonstrated the presence of α-smooth-muscle-actin-positive spindle cells expanding the intima, with few inflammatory cells. We noted an absence of proliferating cell nuclear antigen activity and TUNEL-positive cells in both groups. We observed prominent myocardial interferon-γ gene expression only in Group 1. Conclusion: Despite differences in myocardial interferon-γ gene expression, the histology and severity of the vascular lesions in CAV did not vary significantly with different histoincompatibilities or treatment protocols. These results suggest that the origin of CAV cannot be determined by histology alone. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|