Oxidized LDL stimulates matrix metalloproteinase-1 expression in human vascular endothelial cells.
It has been well documented that acute myocardial infarction is triggered by disruption of atherosclerotic plaques. Immunocytochemistry studies have shown that matrix metalloproteinase-1 (MMP-1) is specifically expressed by cells present in atherosclerotic plaques, including luminal and neovascular endothelial cells. Since MMP-1 degrades type I collagen, a major type of collagen in atherosclerotic lesions, it is likely that MMP-1 is involved in promoting destabilization of plaques. To date, however, the stimulatory factors that induce MMP-1 expression in endothelial cells have not been well defined. In the present study, we found that oxidized low density lipoprotein (LDL) stimulated MMP-1 release from both human umbilical vein and aortic endothelial cells. We also found that oxidized LDL markedly stimulated MMP-1 expression in these cells and that the degree of LDL oxidation was positively correlated with the level of MMP-1 mRNA expression. Furthermore, our data showed that stimulated MMP-1 secretion was inhibited by actinomycin D and that the nascent MMP-1 mRNA synthesis was stimulated by oxidized LDL, indicating that oxidized LDL activated transcription of the MMP-1 gene. Finally, both zymography and activity assays demonstrated that collagenase activity in conditioned medium was stimulated by oxidized LDL. Taken together, these results have shown for the first time that oxidized LDL stimulates MMP-1 transcription and secretion by vascular endothelial cells, suggesting that oxidized LDL may be a potent stimulator for MMP-1 expression in atherosclerotic plaques, thus promoting plaque rupture.
Huang
Y
Y
Division of Endocrinology, Diabetes, and Medical Genetics, Department of Medicine, Medical University of South Carolina, and the Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC 29403, USA.
Mironova
M
M
Lopes-Virella
M F
MF
D001161:Arteriosclerosis / Q000201:enzymology; D002364:Caseins / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013379:Substrate Specificity; D015533:Transcriptional Activation / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology
D002364:Caseins; D017077:Culture Media, Conditioned; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D017364:Collagenases; D020781:Matrix Metalloproteinase 1