High-level expression of Egr-1 and Egr-1-inducible genes in mouse and human atherosclerosis

To understand the mRNA transcript profile in the human atherosclerotic lesi on, RNA was prepared from the fibrous cap versus adjacent media of 13 patie nts undergoing carotid endarterectomy. cDNA expression arrays bearing 588 k nown genes indicated that lesions express unexpectedly high levels of the e arly growth response gene, Egr-1 (NGFI-A), a zinc-finger transcription fact or that modulates a cluster of stress-responsive genes including PDGF and T GF-beta. Expression of Egr-1 was an average of 5-fold higher in the lesion than in the adjacent media, a result confirmed by RT-PCR, and many Egr-1-in ducible genes were also strongly elevated in the lesion. Time-course analys es revealed that Egr-1 was not induced ex vivo. Immunocytochemistry indicat ed that Egr-1 was expressed prominently in the smooth muscle-actin positive cells, particularly in areas of macrophage infiltration, and in other cell types, including endothelial cells. Induction of atherosclerosis in LDL re ceptor-null mice by feeding them a high-fat diet resulted in a progressive increase in Egr-1 expression in the aorta. Thus, induction of Egr-1 by athe rogenic factors may be a key step in coordinating the cellular events that result in vascular lesions.