Histomorphometric comparison of cardiac allograft vasculopathy in miniature swine.
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 alpha-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-gamma gene expression only in Group 1.


CONCLUSIONS
Despite differences in myocardial interferon-gamma 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.
Houser
Stuart L
SL
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02214, USA.
McMorrow
Isabel M
IM
LeGuern
Christian
C
Schwarze
Margaret L
ML
Fuchimoto
Yasuli
Y
Sachs
David H
DH
Madsen
Joren C
JC
D000818:Animals; D003327:Coronary Disease / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006084:Graft Rejection; D016027:Heart Transplantation / Q000276:immunology*; D006648:Histocompatibility; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015335:Molecular Probes; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D013556:Swine, Miniature
D015335:Molecular Probes; D007371:Interferon-gamma