Macrophage depletion alters vein graft intimal hyperplasia

Background. The principal cause of vein graft failure is intimal hyperplasia (IH); however; irs etiology remains unclear. In a rat model of vein graft IH we have observed prolonged transmural macrophage infiltration, lending us to hypothesize that these cells regulate IH. To test this, we used liposome-encapsulated dichloromethylene bisphosphonate (L-Cl2MBP) to deplete rat macrophages and observed the effects on IH. Methods. Epigastric vein-to-femoral artery grafts were microsurgically placed in male Lewis rats that had been intravenously injected with L-Cl2MBP, phosphate-buffered saline solution liposomes, or phosphate-buffered saline solution alone 2 days before surgery. Several animals in each group received a second equivalent close at 2 weeks. Grafts, contralateral epigastric veins, spleens, and livers were harvested at 1, 2 and 4 weeks for histologic examination, immunohistochemistry, and transmission electron microscopy. Results. In the L-Cl2MBP-treated animals splenic and hepatic macrophages were greatly reduced confirming the efficacy of the agent. At 1 to 2 weeks graft macrophages were significantly decreased and there was a trend toward decreased IH. At 4 weeks macrophage members were normal and IH development had resumed. In contrast, the 4-week grafts treated with 2 doses of L-Cl2MBP had fewer macrophages and displayed severely attenuated IH. Conclusions. The results indicate a suppression of IH as macrophages are depleted, with a resumption of the process as macrophages repopulate the graft.