Regulation of leucocyte-endothelial interactions of special relevance to atherogenesis

1. The cellular events underlying atherosclerosis include the accumulation of lipid-laden monocytes in the neointima. This process is associated with the expression of adhesion proteins and chemokines by the endothelium, in a manner similar to that seen after the administration of pro-inflammatory cytokines to endothelial cells. 2. The processes that limit endothelial responses to proinflammatory cytokines are, therefore, the subject of this paper. Evidence is presented that the cytokine TGF-beta exerts a tonic inhibitory influence on endothelial responses. Furthermore, the smooth muscle cells adjacent to endothelial cells have a similar effect to exogenous TGF-beta and this suggests that these two cells form a functional interactive unit. Finally, the atheroprotective lipid fraction, high-density lipoproteins (HDL), also inhibits endothelial activation. The mechanism of effect of HDL that appears separate from its traditional role in cholesterol transport may yield novel insights into atheroprotection.