Smooth muscle cell migration into intima and adventitia during development of transplant vasculopathy

Smooth muscle cell (SMC) migration from the medial layer into the intima is a characteristic feature of transplant vasculopathy and is thought to be regulated by locally produced cytokines. We studied the expression of smooth muscle alpha-actin, PDGF B-ligand and, PDGF alpha- and beta-receptors in rat aortic allografts with transplant vasculopathy using immunohistochemistry. At two weeks, an intense expression of PDGF B-ligand and, PDGF alpha- and beta-receptors was found in the neointima and adventitia. Medial SMC expression decreased with time in parallel with accumulation of smooth muscle alpha-actin in the neointima and adventitia. PDGF expression persisted in the adventitia. Prolonged ischemic storage time resulted in an increase in the number of alpha-actin-positive SMCs in the intima of syngeneic grafts. These data indicate that SMCs migrate into both the intima and adventitia. This migration may be induced, at least in part, by PDGF produced by graft invading monocyte-derived macrophages.