Endothelial expression of matrix metalloproteinases has been implicated in angiogenesis and endothelial cell proliferation. Recently, it has been shown that high-density lipoproteins (HDLs) promote angiogenesis. In the present study, we investigated the effects of native HDLs on the expression of several proteases and their inhibitors in human umbilical vein endothelial cells. We show that ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin motif) was potently induced by incubation with lipopolysaccharide or tumor necrosis factor-alpha and that the expression was significantly reduced in the presence of HDL subfraction 3. Since ADAMTS-1 has recently been shown to inhibit endothelial cell proliferation, the result of the present work may represent a new mechanism by which HDL could have a positive effect on endothelial cell and vascular wall function.