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.
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: Maria G Frid; Jacqueline A Brunetti; Danielle L Burke; Todd C Carpenter; Neil J Davie; John T Reeves; Mark T Roedersheimer; Nico van Rooijen; Kurt R Stenmark Journal: Am J Pathol Date: 2006-02 Impact factor: 4.307
Authors: Jonathan P Rehfuss; Kenneth M DeSart; Jared M Rozowsky; Kerri A O'Malley; Lyle L Moldawer; Henry V Baker; Yaqun Wang; Rongling Wu; Peter R Nelson; Scott A Berceli Journal: Circ Genom Precis Med Date: 2018-03
Authors: Dimitrios Mitsouras; Ming Tao; Margreet R de Vries; Kaspar Trocha; Oscar R Miranda; Praveen Kumar Vemula; Kui Ding; Amir Imanzadeh; Frederick J Schoen; Jeffrey M Karp; C Keith Ozaki; Frank J Rybicki Journal: Acta Radiol Date: 2018-01-29 Impact factor: 1.990