PROTECTION FROM OXIDIZED LDG-INDUCED LEUKOCYTE ADHESION TO MICROVASCULAR AND MACROVASCULAR ENDOTHELIUM IN-VIVO BY VITAMIN-C BUT NOT BY VITAMIN-E

Background The ability of oxidized LDL (oxLDL) to stimulate leukocyte- endothelium interaction is considered to be an important aspect of its proatherogenic action. Using intravital fluorescence microscopy in th e dorsal skinfold chamber model in hamsters, we have previously shown that systemic administration of oxLDL stimulates leukocyte adhesion to microvascular endothelium through a mechanism that involves the gener ation and action of reactive oxygen species (ROS). Methods and Results Through the combined use of scanning electron microscopy and intravit al microscopy in the same animal model, we demonstrate that oxLDL-indu ced leukocyte adhesion is not confined to the microcirculation but can also be observed on aortic endothelium. OxLDL-induced leukocyte adhes ion to both microvascular and macrovascular endothelium was almost ent irely prevented by pretreatment of the hamsters with dietary or intrav enous vitamin C, which has the capacity to scavenge and neutralize ROS (arterioles: 20.51+/-16.4 cells/mm(2) [diet] and 16.3+/-23.8 cells/mm (2) [IV] versus 74.2+/-47.5 cells/mm(2) [control, P<.01]; aorta: 1.0+/ -0.4 cells/mm(2) [diet] and 1.1+/-0.5 cells/mm(2) [IV] versus 14.7+/-6 .0 cells/mm(2) [control, P<.01], 15 minutes after oxLDL, n=7 animals p er group). Vitamin C pretreatment also completely prevented oxLDL-indu ced leukocyte-platelet aggregate formation in the bloodstream but did not affect leukocyte rolling along the microvascular endothelium. No i nhibitory effect on any of the studied parameters was observed as a re sult of pretreatment of the animals with the lipid-soluble antioxidant s vitamin E and probucol. Conclusions The protective effects of vitami n C on oxLDL-induced leukocyte adhesion and aggregate formation were s een at vitamin C plasma levels that can easily be reached in humans by diet or supplementation, suggesting that this could be one of the mec hanisms by which vitamin C contributes to the well-documented protract ion of atherogenesis as observed in large epidemiological surveys.