Enzymatically degraded low density lipoproteins are more potent inducers of egr-1 mRNA than oxidized or native low density lipoproteins

Objectives: 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. Design and 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 μg 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 μg/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.