Contribution of pre-existing vascular disease to allograft vasculopathy in a murine model.
Allograft vasculopathy (AV) has emerged as a major obstacle for long-term graft survival after cardiac transplantation. The shortage of donor hearts has meant fewer restrictions have been placed on acceptable hearts over the past few years resulting in an increase in the number of older hearts in the donor pool. This increase has subsequently led to the increase of donor hearts containing pre-existing disease. The importance of this pre-existing donor vascular disease in AV outcomes remains controversial. In this study we address this by taking advantage of the fact that B6 Apolipoprotein-E knockout mice develop atherosclerotic lesions in their aortic tracts that closely model human naturally occurring vascular disease. By using these mice as donors, we transplant known levels of pre-existing disease into fully disparate (C3H) recipients. Cyclosporin A is used to prevent acute rejection and allow for allograft vasculopathy. We found that pre-existing lesions are retained in this model after transplantation and that they contribute to increase in lesion size and to increased lumenal narrowing. The de novo AV lesions overlay the pre-existing lesions and this leads to areas of eccentric lesion formation in the vessels with likely accompanying exacerbation of flow perturbation.
Zaki
Amr M
AM
Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
Hirsch
Gregory M
GM
Lee
Timothy D G
TD
D000818:Animals; D001011:Aorta / Q000473:pathology* / Q000637:transplantation*; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D016572:Cyclosporine / Q000627:therapeutic use; D004195:Disease Models, Animal; D005487:Foam Cells / Q000473:pathology; D006084:Graft Rejection / Q000517:prevention & control; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000473:pathology; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D017540:Tunica Media / Q000378:metabolism / Q000473:pathology; D014652:Vascular Diseases / Q000209:etiology* / Q000473:pathology*
D001057:Apolipoproteins E; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D016572:Cyclosporine