Enzymatically degraded low density lipoproteins are more potent inducers of egr-1 mRNA than oxidized or native low density lipoproteins.
OBJECTIVE
The transcription factor early growth response gene-1 (Egr-1) may contribute to atherosclerosis by inducing genes that mediate inflammation and thrombosis. Egr-1 mRNA is highly expressed in human atherosclerotic lesions. Enzymatic modification transforms LDL into atherogenic molecules (E-LDL) which are also present in atherosclerotic lesions. We have investigated whether E-LDL induces egr-1 mRNA in human monocytes.


METHODS
Mono-Mac-6 cells were incubated with E-LDL, oxidized (Ox-LDL) and native LDL (N-LDL). Egr-1 mRNA expression was followed by quantitative RT-PCR.


RESULTS
E-LDL (25 microg cholesterol/mL) induced egr-1 mRNA maximally within 1 h and were 2.3 and 3.6 fold (p < 0.05) more effective than Ox-LDL or N-LDL. At a concentration of 10 microg/mL cholesterol, E-LDL were twofold less effective.


CONCLUSIONS
These results show that E-LDL are potent inducers of egr-1 mRNA and may therefore represent a link between lipoproteins trapped in the subendothelium and enhanced expression of egr-1 in human atherosclerotic lesions.
Stoyanova
E
E
Abteilung Klinische Chemie, Georg-August-Universität Göttingen, Göttingen, Germany.
Tesch
A
A
Armstrong
V W
VW
Wieland
E
E
D001161:Arteriosclerosis / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D014157:Transcription Factors; C099252:oxidized low density lipoprotein