Alloimmune-Mediated Vascular Remodeling of Human Coronary Artery Grafts in Immunodeficient Mouse Recipients Is Independent of Preexisting Atherosclerosis

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Abstract
Vascular remodeling rather than intimal thickening is the most important determinant of luminal loss in cardiac graft arteriosclerosis. The impact of donor-transmitted atherosclerotic lesions on alloimmune-mediated arterial injury in an experimental setting is not known. We investigated this issue in a chimeric model of human coronary artery grafts to immunodeficient mouse recipients reconstituted with allogeneic human peripheral blood mononuclear cells. Rejecting grafts demonstrated robust intimal expansion, outward vascular remodeling, and variable lumen loss. There was no significant relationship between preexistent atherosclerosis, gender, and age of the artery donors vs. the degree of alloimmune-induced changes in vessel morphology. Our experimental findings, in a system without the potentially confounding variable of immunosuppressive drugs, are in agreement with the majority of clinical studies that alloimmune-mediated intimal injury and vascular remodeling is independent of preexisting coronary atherosclerosis. Our results support the concept of extending the criteria for organ donors to include modest coronary atherosclerosis.

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