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Updated: Jun 3, 2026
Heterotopic Cervical Heart Transplantation in Mice
Published on: August 25, 2015
Coronary artery disease from isolated non-H2-determined incompatibilities in transplanted mouse hearts
Paul S Russell1, Catharine M Chase, Joren C Madsen
1Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA. psrussell@partners.org
Insights
Coronary artery vasculopathy (CAV) can occur in heart transplants due to non-major histocompatibility complex (MHC) incompatibilities alone. Presensitization significantly worsens this vascular disease, even with sparse antigen expression.
Area of Science:
- Transplantation immunology
- Vascular biology
- Graft rejection mechanisms
Background:
- Traditional studies link transplant vascular disease to major histocompatibility complex (MHC) disparities.
- This research investigates coronary artery vasculopathy (CAV) in mouse heart transplants with isolated, non-MHC incompatibilities.
Purpose of the Study:
- To determine if non-MHC incompatibilities can independently cause coronary artery vasculopathy (CAV) in transplanted hearts.
- To assess the impact of presensitization on CAV development in non-MHC incompatible transplants.
Main Methods:
- Mice with HY, H4, or H60 incompatibilities were used for heart transplantation.
- Congenic strains or transgenic methods were employed to establish H60 incompatibility.
- Transplant survival and the incidence of CAV were evaluated histologically.
Main Results:
- Advanced CAV developed by 56 days in HY and H4 incompatible heart transplants, which also rejected skin grafts.
- H60 incompatibility alone caused minimal CAV and did not lead to skin graft rejection.
- Presensitization with H60 and HY antigens significantly exacerbated CAV in H60 incompatible heart transplants.
Conclusions:
- Non-MHC incompatibilities alone can induce CAV, even with limited antigen expression on cardiac tissue.
- Presensitization dramatically increases the severity of CAV in non-MHC incompatible transplants.
- This suggests non-MHC incompatibilities may contribute to vascular disease in human transplants, including those matched for MHC.
Background:
Most studies of vascular disease in transplanted organs have used combinations involving disparities determined by genes of the major histocompatibility complex (MHC). This report describes examples of coronary vascular disease occurring in transplanted mouse hearts involving isolated, non-H2-determined incompatibilities.
Methods:
Mice, incompatible in respect of HY, H4, or H60, were selected. For H60, the incompatibility depended on breeding congenic pairs or the introduction of H60 by transgenic methods because the latter method results in more widespread expression. Transplant survival was determined, and the appearance and prevalence of coronary artery vasculopathy (CAV) was established by appropriate histologic methods.
Results:
Advanced changes of CAV were found at 56 days in transplants involving incompatibilities confined to HY or H4. In both combinations, skin grafts were also rejected. H60 incompatibility does not result in skin graft rejection and only a minority of heart transplants shows evidence of CAV. If heart transplants are preceded by skin grafts bearing both H60 and HY incompatibilities to promote "help" in generating immunity, H60 incompatible hearts develop advanced CAV. Heart transplants in all non-MHC categories ostensibly survive in excellent condition throughout this period despite their CAV.
Conclusions:
CAV can develop as a consequence of non-MHC incompatibilities alone and even when antigens are sparsely expressed on cardiac tissue. Presensitization leads to much more severe vascular disease. Human leukocyte antigen compatible kidney transplants may also develop vascular disease and patients manifesting reactivity to MHC antigens should also be more prone to develop vascular disease because of undetectable non-MHC incompatibilities.
