Document Detail

Endothelial dysfunction and denudation in rat aortic allografts.
MedLine Citation:
PMID:  11145935     Owner:  NLM     Status:  MEDLINE    
Clinical evidence suggests that early endothelial cell (EC) dysfunction may predict the development of graft vascular disease. We wished to assess the early functional and morphological changes in the graft endothelium in a commonly used animal model of graft vascular disease, the rat aortic interposition allograft model. To assess graft EC function, regulation of vascular tone by ECs was monitored in aortic rings from grafts harvested at various times after transplantation (Tx). EC morphology was assessed by silver staining, which was followed by en face inspection of the luminal side of the grafts. Acetylcholine-induced EC-dependent vasorelaxation was reduced in allografts at post-Tx days 7 and 14, whereas in syngeneic grafts EC-dependent relaxation was unaffected at any time after Tx. In separate grafts collected at the same time points, massive leukocyte adhesion at post-Tx day 7 and EC denudation at days 14 and 28 were evident in allografts but not in syngeneic grafts. At post-Tx day 56 (a time at which vessel wall remodeling is pronounced in this model), an intact EC layer covered the grafts. EC dysfunction and morphological changes were prevented by immunosuppression of recipient rats with cyclosporine. Our study shows that Tx-induced EC dysfunction in rat aortic allografts can be observed within 1 week of Tx in rat aortic allografts and that this is occurring concomitantly with enhanced leukocyte adhesion to the graft ECs. These changes occur before any other morphological or functional changes described thus far in this model and appear to be immune-driven. Taken together, these results show that Tx-induced early EC dysfunction, as described in patients, may be studied in the model of rat aortic Tx.
E Andriambeloson; M Bigaud; E O Schraa; T Kobel; V Lobstein; C Pally; H G Zerwes
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  21     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-01-12     Completed Date:  2001-02-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  67-73     Citation Subset:  IM    
Novartis Pharma AG, Transplantation Research, Basel, Switzerland.
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MeSH Terms
Aorta / pathology,  physiopathology*,  transplantation*
Endothelium, Vascular / pathology*,  physiopathology*
Graft vs Host Disease / pathology,  physiopathology
Muscle Relaxation
Muscle, Smooth, Vascular / pathology,  physiopathology
Rats, Inbred Dahl
Rats, Inbred Lew
Silver Staining
Transplantation, Homologous / adverse effects,  pathology

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