Recipient cells form the intimal proliferative lesion in the rat aortic model of allograft arteriosclerosis

Abstract

Chronic rejection is the leading cause of late graft loss following solid organ transplantation and is characterized by a vasculopathy referred to as allograft arteriosclerosis. While the etiology of allograft arteriosclerosis remains unknown, it has been hypothesized that migration of donor medial smooth muscle cells into the intimal compartment is responsible for the formation of the occlusive lesion (neointima). In this study we have used aortic interposition grafts between fully histoincompatible rat strains (Brown Norway and Lewis) to investigate the origin of the neointimal cells. Three transplant paradigms were used: BN to Lew, Lew to BN and BN to Lew with immunosuppression. Neointimal cells were isolated from aortic transplant tissue through an EDTA wash/mechanical stripping technique. We have developed polymerase chain reaction primers to the MHC1 allele that are specific to each rat strains' DNA. Polymerase chain reaction analysis, using the strain-specific primers and purified neointimal cell DNA from transplanted aortic tissue from all three experimental groups, demonstrated that the neointimal cells are of recipient, and not donor origin.