title: Macrophage depletion alters vein graft intimal hyperplasia.
abstract: BACKGROUND
  The principal cause of vein graft failure is intimal hyperplasia (IH); however, its etiology remains unclear. In a rat model of vein graft IH we have observed prolonged transmural macrophage infiltration, leading 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 dose 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 numbers 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.
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine, Madison, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Hoch
authors.forename: V K
authors.initials: VK
authors.lastname: Stark
authors.forename: N
authors.initials: N
authors.lastname: van Rooijen
authors.forename: J L
authors.initials: JL
authors.lastname: Kim
authors.forename: M P
authors.initials: MP
authors.lastname: Nutt
authors.forename: T F
authors.initials: TF
authors.lastname: Warner
mesh_terms: D000818:Animals; D006965:Hyperplasia; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008854:Microscopy, Electron; D009000:Monocytes / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D014680:Veins / Q000473:pathology / Q000637:transplantation* / Q000648:ultrastructure