Two-dimensional maps of short-term albumin uptake by the immature and mature rabbit aortic wall around branch points.

In children, aortic lipid deposition develops in triangular regions of the wall downstream of branch points, whilst in adults these regions are particularly free of disease. Comparable age-related patterns occur in rabbit aortas. They may be explained by patterns of wall permeability to circulating macromolecules: along the longitudinal midline through branches, permeability is greater downstream than upstream in immature rabbits, but is greater upstream at later ages. Here we have mapped permeability in detail around such branches, not just along the midline. Short-term uptake of rhodamine-labeled albumin, measured using digital imaging fluorescence microscopy of serial sections, was greatest in an approximately triangular region downstream of immature branches, but in mature animals it was greater upstream, particularly away from the midline, and in streaks to the side of branches. Hence the maps are consistent with earlier permeability data and closely resemble the patterns of disease.

Effect of genistein and daidzein on platelet aggregation and monocyte and endothelial function.

There has been much recent interest in the cardiovascular benefits of dietary isoflavones. The aim of the present in vitro studies was to investigate potential anti-thrombogenic and anti-atherogenic effects of the isoflavones genistein and daidzein in platelets, macrophages and endothelial cells. Pre-treatment with either isoflavone inhibited collagen-induced platelet aggregation in a dose-dependent manner. In a macrophage cell line (RAW 264.7) activated with interferon gamma plus lipopolysaccharide, both isoflavones were found to inhibit NO production and tumour necrosis factor alpha (TNF-alpha) secretion dose-dependently, but they did not affect mRNA levels for inducible nitric oxide synthase and cyclo-oxygenase-2. Both isoflavones also dose-dependently decreased monocyte chemoattractant protein-1 secretion induced by TNF-alpha in human umbilical vein endothelial cells. Compared with daidzein, genistein exerted greater inhibitory effects for all parameters studied. The present data contributes to our knowledge on the molecular mechanisms by which isoflavones may protect against coronary artery disease. Further studies are required to determine whether the effects of isoflavones observed in the current in vitro studies are relevant to the aetiology of coronary artery disease in vivo.