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Updated: Jun 21, 2026
Mouse Model of Alloimmune-induced Vascular Rejection and Transplant Arteriosclerosis
Published on: May 17, 2015
Contribution of pre-existing vascular disease to allograft vasculopathy in a murine model
Amr M Zaki1, Gregory M Hirsch, Timothy D G Lee
1Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
Insights
Pre-existing vascular disease in donor hearts worsens allograft vasculopathy after cardiac transplantation. This leads to larger lesions and narrowed vessels, impacting long-term graft survival.
Area of Science:
- Cardiovascular Research
- Transplantation Immunology
- Vascular Biology
Background:
- Allograft vasculopathy (AV) is a primary cause of graft loss after heart transplantation.
- Increased use of older donor hearts with pre-existing disease is common due to donor shortages.
- The impact of donor-specific vascular disease on AV development is not well understood.
Purpose of the Study:
- To investigate the role of pre-existing donor vascular disease in the development of allograft vasculopathy.
- To determine if naturally occurring atherosclerotic lesions in donor aortas influence post-transplant AV outcomes.
Main Methods:
- Utilized Apolipoprotein-E knockout mice (B6) as donors to introduce controlled atherosclerotic lesions.
- Transplanted B6 donor hearts into fully disparate C3H recipients.
- Administered Cyclosporin A to prevent acute rejection and facilitate AV development.
Main Results:
- Pre-existing atherosclerotic lesions were retained in transplanted allografts.
- Donor vascular disease significantly increased the size of AV lesions and lumenal narrowing.
- De novo AV lesions superimposed on pre-existing lesions caused eccentric lesion formation and exacerbated flow perturbations.
Conclusions:
- Pre-existing vascular disease in donor hearts is a critical determinant of allograft vasculopathy severity.
- This finding highlights the importance of donor vascular health in improving long-term cardiac allograft survival.
Abstract:
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.
