Mechanism of Dacron-activated monocytic cell oxidation of low density lipoprotein

Purpose: Oxidized lipids are believed to contribute to atherogenesis and ma y play a role in the development of anastomotic intimal hyperplasia in pros thetic vascular grafts. This study examines the hypothesis that clinically relevant graft material activates monocytes to oxidize low density lipoprot ein (LDL). Methods: LDL and Dacron or expanded polytetrafluoroethylene (ePTFE) graft m aterial were incubated in the presence of U937 cells, a monocytic cell line . LDL oxidation was measured by conjugated dienes, lipid peroxides, thiobar bituric acid-reacting substances, and electrophoretic mobility. Cell produc tion of superoxide was measured by ferricytochrome c reduction. Metal ion r equirement was assessed with the metal chelators, ethylenediaminetetra-acid ic acid, deferoxamine, and bathocuproinedisulfonic acid. To determine wheth er human monocytes were capable of being activated by Dacron graft material to oxidize LDL, freshly isolated peripheral blood monocytes were also stud ied. Results: Incubation of LDL with U937 cells and Dacron increased LDL oxidati on by 5- to 20-fold. LDL incubated with ePTFE or U937 cells alone resulted in minimal oxidation. Dacron graft increased U937 cell production of sulper oxide by 4-fold, whereas ePTFE had no effect. Superoxide dismutase inhibite d Dacron-activated U937 cell oxidation of LDL by greater than 50%, which in dicates a role for superoxide. Ethylenediaminetetra-acidic acid, deferoxami ne, and bathocuproinedisulfonic acid each inhibited Dacron-activated U937 c ell oxidation of LDL. Human peripheral blood monocytes were activated by Da cron graft material to oxidize LDL; superoxide dismutase inhibited Dacron-a ctivated human monocytic oxidation of LDL, which suggests a role for supero xide. Conclusion: These results suggest that Dacron graft material activates mono cytes to oxidize LDL by a mechanism that involves superoxide and requires i ron and copper ions. Our work suggests a mechanism by which lipids that hav e been deposited within implanted vascular grafts may become oxidized. Oxid ized lipids may contribute to the cellular dysfunction that results in anas tomotic intimal hyperplasia and graft failure.