High levels of homocysteine induce a sustained injury on arterial endothelial cells which accelerates the development of thrombosis and atherosclerosis. Some of the described effects of homocysteine on endothelial cells are features shared with an antiangiogenic response. Therefore, we studied the effects of homocysteine on key steps of angiogenesis using bovine aorta endothelial cells as a model. Homocysteine decreased proliferation and induced differentiation. Furthermore. 5mM homocysteine produced strong inhibitions of matrix metalloproteinase-2 and urokinase. two proteolytic activities that play a key role in extracellular matrix re-modeling, and decreased migration and invasion. other two key steps of angiogenesis, This study demonstrates that homocysteine can inhibit several steps of the angiogenic process. (C) 2002 Elsevier Science (USA). All rights reserved.