Oxidized LDL stimulates matrix metalloproteinase-1 expression in human vascular endothelial cells

It has been well documented that acute myocardial infarction is triggered b y disruption of atherosclerotic plaques. Immunocytochemistry studies have s hown that matrix metalloproteinase-1 (MMP-1) is specifically expressed by c ells present in atherosclerotic plaques, including luminal and neovascular endothelial cells. Since MMP-1 degrades type I collagen, a major type of co llagen in atherosclerotic lesions, it is likely that MMP-1 is involved in p romoting destabilization of plaques. To date, however, the stimulatory fact ors that induce MMP-1 expression in endothelial cells have not been well de fined. In the present study, we found that oxidized low density lipoprotein (LDL) stimulated MMP-1 release from both human umbilical vein and aortic e ndothelial cells. We also found that oxidized LDL markedly stimulated MMP-1 expression in these cells and that the degree of LDL oxidation was positiv ely correlated with the level of MMP-1 mRNA expression. Furthermore, our da ta showed that stimulated MMP-1 secretion was inhibited by actinomycin D an d that the nascent MMP-1 mRNA synthesis was stimulated by oxidized LDL, ind icating that oxidized LDL activated transcription of the MMP-1 gene. Finall y, both zymography and activity assays demonstrated that collagenase activi ty in conditioned medium was stimulated by oxidized LDL. Taken together, th ese results have shown for the first time that oxidized LDL stimulates MMP- 1 transcription and secretion by vascular endothelial cells, suggesting tha t oxidized LDL may be a potent stimulator for MMP-1 expression in atheroscl erotic plaques, thus promoting plaque rupture.