Vascular smooth muscle cells and neointimal hyperplasia in chronic transplant rejection.

Intimal hyperplasia is the characteristic pathological hallmark in the arterial tree of chronically rejecting solid organ grafts. Mechanisms underlying the development of this lesion are poorly understood. One strongly held hypothesis is that vascular smooth muscle cells (vs.mcs) migrate from the medial layer of arteries contained within the graft into the intima forming the "neointima" characteristic of intimal hyperplasia. This study investigated this theory in a rat aortic allograft model of intimal hyperplasia. It also examined the possibility, using a combination of immunocytochemistry and electron microscopy, that aortic vs.mcs may undergo a phenotypic change during this process. Intimal area in syngeneic grafts was 3509 +/- 4325 pixels (n = 5) compared with 240,896 +/- 87,042 in allogenic grafts (n = 9, P < 0.001) 12 weeks after transplantation. At that time medial nuclear density was markedly reduced in the same allografts compared with corresponding syngeneic grafts (0.83 +/- 0.14 versus 2.64 +/- 0.60, P < 0.001, respectively). The most striking finding was that there was strongly positive staining for alpha-actin cells in the neointima in association with an almost acellular medial layer. Immunocytochemical staining also demonstrated the presence of beta-actin cells in the neointima of allografts while electron microscopy showed these cells to be secretory in phenotype. These results support the hypothesis that vs.mcs form an important component of the lesion of intimal hyperplasia and also propose that a phenotypic change may occur in these cells once they are present in the neointima.