MONOCYTE CHEMOTACTIC PROTEIN-1 EXPRESSION IS ASSOCIATED WITH THE DEVELOPMENT OF VEIN GRAFT INTIMAL HYPERPLASIA

Infiltration of immunologically active cells into vein grafts is conco mitant with the development of intimal hyperplasia (IH) and often lead s to obliterative stenosis and graft failure. Previous work has demons trated the prolonged presence of monocytes and macrophages in vein raf ts. The a stimuli attracting these macrophages remain unidentified. Mo nocyte chemotactic protein-1 (MCP-1), a potent and specific chemokine for monocytes/macrophages, is secreted by smooth muscle cells, endothe lial cells, fibroblasts, and leukocytes, all of which are present in g rafted veins. In this study, we examined the temporal profile of MCP-1 gene expression in rat vein grafts by using reverse transcription-pol ymerase chain reaction (PCR) and immunohistochemistry. Epigastric vein -to-femoral artery bypass grafts were microsurgically placed and harve sted at various time points after grafting. Histological analysis conf irmed the consistent development of IH. PCR was performed and relative levels of MCP-1 quantified by autoradiography. Our results show that MCP-1 mRNA levels in creased 28-fold by 4 hours after grafting and up to 117-fold by 1 week. After this time MCP-1 mRNA levels decreased; no netheless, even at 8 weeks after grafting, message levels remained ele vated 7-fold above baseline. Immunoreactive MCP-1 protein and ED1+ mac rophages were detected at all time points; the degree of immunostainin g correlated with MCP-1 mRNA levels. Our results support the hypothesi s that upregulation of MCP-1 gene expression in vein grafts results in the recruitment of monocytes and tissue macrophages to the vein wall. which leads to M. The correlation between monocyte/macrophage infiltr ation and IH suggests a critical role for these cells in IH developmen t.