Vein graft intimal hyperplasia: leukocytes and cytokine gene expression

Intimal hyperplasia (IH), a cause of early graft failure, may be regulated by leukocyte-elaborated cytokines. We investigated leukocyte infiltration and cytokine gene expression in vein grafts.

Epigastric vein to femoral artery grafts were performed in Lewis rats and harvested on day 4 and weeks 1, 2, 4, 8, and 12. Neointimal areas were measured by computerized planimetry. Immunoperoxidase staining identified for macrophages, CD4+, CD8+, and major histocompatibility complex class II+ cells. Graft RNA was used in reversetranscription-polymerase chain reaction with interleukin (IL)-1 alpha, IL-2R, monocyte chemoattractant protein-1, and transforming growth factor-beta primers.

IH was measurable at 2 weeks; the perianastomotic regions displayed greater IH than the midgraft (p < 0.05). MANOVA indicated strong location (p = 0.0001) and time (p = 0.0009) effects. Immunocytochemistry showed inflammatory infiltrates from 4 days to 4 major histocompatibility complex class II+ and primarily monocyte/macrophages, with less frequent T lymphocytes (CD4+ > CD8+). IL-1 alpha messenger RNA is expressed early, disappearing after 4 weeks. Monocyte chemoattracta t protein-1 mRNA is constitutively expressed, with up-regulation at 4 days to 4 weeks. IL-2R mRNA levels fluctuate; transforming growth factor-beta is always expressed, peaking at 4 days to 4 weeks.

Gene expression of cytokines thought to modulate IH is up-regulated early in vein grafts. This coincides with graft infiltration by activated leukocytes before and during the development of IH.