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 s trongly held hypothesis is that vascular smooth muscle cells (vs.mcs) migrate hom the medial layer of arteries contained within the graft in to the intima forming the ''neointima'' characteristic of intimal hype rplasia. 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 ao rtic vs.mcs may undergo a phenotypic change during this process. Intim al area in syngeneic grafts was 3509+/-4325 pixels (n=5) compared with 240,896+/-87,042 in allogeneic grafts (n=9, P<0.001) 12 weeks after t ransplantation, At that time medial nuclear density was markedly reduc ed in the same allografts compared with corresponding syngeneic grafts (0.83+/-0.14 versus 2.64+/-0.60, P<0.001, respectively). The most str iking finding was that there was strongly positive staining for alpha- actin cells in the neointima in association with an almost acellular m edial layer. Immunocytochemical staining also demonstrated the presenc e of beta-act-in cells in the neointima of allografts while electron m icroscopy showed these cells to be secretory in phenotype. These resul ts support the hypothesis that vs.mcs form an important component of t he lesion of intimal hyperplasia and also propose that a phenotypic ch ange may occur in these cells once they are present in the neointima.