Mechanism of dacron-activated monocytic cell oxidation of low density lipoprotein.

PURPOSE

Oxidized lipids are believed to contribute to atherogenesis and may play a role in the development of anastomotic intimal hyperplasia in prosthetic vascular grafts. This study examines the hypothesis that clinically relevant graft material activates monocytes to oxidize low density lipoprotein (LDL).

METHODS

LDL and Dacron or expanded polytetrafluoroethylene (ePTFE) graft material were incubated in the presence of U937 cells, a monocytic cell line. LDL oxidation was measured by conjugated dienes, lipid peroxides, thiobarbituric acid-reacting substances, and electrophoretic mobility. Cell production of superoxide was measured by ferricytochrome c reduction. Metal ion requirement was assessed with the metal chelators, ethylenediaminetetra-acidic acid, deferoxamine, and bathocuproinedisulfonic acid. To determine whether human monocytes were capable of being activated by Dacron graft material to oxidize LDL, freshly isolated peripheral blood monocytes were also studied.

RESULTS

Incubation of LDL with U937 cells and Dacron increased LDL oxidation by 5- to 20-fold. LDL incubated with ePTFE or U937 cells alone resulted in minimal oxidation. Dacron graft increased U937 cell production of superoxide by 4-fold, whereas ePTFE had no effect. Superoxide dismutase inhibited Dacron-activated U937 cell oxidation of LDL by greater than 50%, which indicates a role for superoxide. Ethylenediaminetetra-acidic acid, deferoxamine, and bathocuproinedisulfonic acid each inhibited Dacron-activated U937 cell oxidation of LDL. Human peripheral blood monocytes were activated by Dacron graft material to oxidize LDL; superoxide dismutase inhibited Dacron-activated human monocytic oxidation of LDL, which suggests a role for superoxide.

CONCLUSION

These results suggest that Dacron graft material activates monocytes to oxidize LDL by a mechanism that involves superoxide and requires iron and copper ions. Our work suggests a mechanism by which lipids that have been deposited within implanted vascular grafts may become oxidized. Oxidized lipids may contribute to the cellular dysfunction that results in anastomotic intimal hyperplasia and graft failure.