Dysfunction of arterial endothelial cells (EC) leading to adherence of circulating leucocytes (WBC) is a pivotal step in atherogenesis, preceding fatty streak formation. The attachment process is mediated at least in part by inducible endothelial-leucocyte adhesion molecules (ELAMs) on the EC surface which interact with WBC counterreceptors. Expression of VCAM-1, a monocyte selective adhesion molecule, by IL-1 and TNF stimulated vascular EC in vitro was shown to be inhibited by a thiol antioxidant (pyrrolidine dithiocarbamate, PDTC). In this study we analyzed the effect of PDTC administered to cholesterol-fed rabbits, on WBC attachment to lesion-prone sites of the aorta using SEM morphometry.
New Zealand White (NZW) rabbits (2-3 kg) were fed 1% cholesterol for 3 d. The day before feeding, venous cannulas were introduced, and PDTC (20 mg/kg) or vehicle (0.1 M PBS) was given twice daily throughout. The animals were euthanatized at 4 d and the aortas pressure perfusion fixed with buffered 2.5% glutaraldehyde after rinse with Ringer‘s solution containing heparin (10 u/ml).