(Circulation. 1995;91:1525-1532.)
© 1995 American Heart Association, Inc.
Articles |
Protection From Oxidized LDL–Induced Leukocyte Adhesion to Microvascular and Macrovascular Endothelium In Vivo by Vitamin C but Not by Vitamin E
From the Institute for Surgical Research (H.-A.L.), University of Munich, Germany; Whitaker Cardiovascular Institute (B.F.), Boston University Medical Center, Boston, Mass; Department of Medical and Physiological Chemistry (A.M.O.), University of Lund, Sweden; Experimental Medicine Inc (K.-E.A.), Princeton, NJ; and San Diego Regional Cancer Center (K.-E.A.), San Diego, Calif.
Correspondence to Hans-Anton Lehr, MD, PhD, Department of Pathology, University of Washington Medical Center, RC-72, 1959 NE Pacific St, Seattle, WA 98195.
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 the 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 generation and action of reactive oxygen species (ROS).
Methods and Results Through the combined use of scanning electron microscopy and intravital microscopy in the same animal model, we demonstrate that oxLDL-induced leukocyte adhesion is not confined to the microcirculation but can also be observed on aortic endothelium. OxLDL-induced leukocyte adhesion to both microvascular and macrovascular endothelium was almost entirely prevented by pretreatment of the hamsters with dietary or intravenous vitamin C, which has the capacity to scavenge and neutralize ROS (arterioles: 20.5±16.4 cells/mm2 [diet] and 16.3±23.8 cells/mm2 [IV] versus 74.2±47.5 cells/mm2 [control, P<.01]; aorta: 1.0±0.4 cells/mm2 [diet] and 1.1±0.5 cells/mm2 [IV] versus 14.7±6.0 cells/mm2 [control, P<.01], 15 minutes after oxLDL, n=7 animals per group). Vitamin C pretreatment also completely prevented oxLDL-induced leukocyte-platelet aggregate formation in the bloodstream but did not affect leukocyte rolling along the microvascular endothelium. No inhibitory effect on any of the studied parameters was observed as a result of pretreatment of the animals with the lipid-soluble antioxidants vitamin E and probucol.
Conclusions The protective effects of vitamin C on oxLDL-induced leukocyte adhesion and aggregate formation were seen at vitamin C plasma levels that can easily be reached in humans by diet or supplementation, suggesting that this could be one of the mechanisms by which vitamin C contributes to the well-documented protraction of atherogenesis as observed in large epidemiological surveys.
Key Words: platelets • probucol • atherogenesis • lipoproteins
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