Neutralizing LDL-induced white blood cell damage: investigation of a new antioxidant route

Abstract

Incorporation of oxidized low-density lipoprotein (ox-LDL) into macrophages adherent to the lumen of vascular tissue is a necessary step in the development of atherosclerotic plaques. Theses regions are characterized by the progressive accumulation of cells, cellular debris, lipid and extracellular matrix material and are found primarily at vascular bifurcations experiencing low levels of blood-flow mediated fluid stress. Macrophage cells found at the core of these plaques are sequestered from circulating anti-oxidants, which could otherwise neutralize damaging ox-LDL. Since regulating the interaction of LDL with macrophages is critical to inhibiting plaque development, the present studies investigated the effectiveness of mechanical and chemical preconditioning in reducing the consequences of oxidative injury mediated by LDL. The results of our studies suggest that intermediate shear stress levels, typical of bifurcated vascular regions, may contribute to LDL mediated macrophage damage. However, oxidative injury may be modulated by pre-incubation with an extracellular source of the free radical scavenger, reduced glutathione (GSH).