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High-level expression of Egr-1 and Egr-1–inducible genes in mouse and human atherosclerosis
Open accessAbstract
To understand the mRNA transcript profile in the human atherosclerotic lesion, RNA was prepared from the fibrous cap versus adjacent media of 13 patients undergoing carotid endarterectomy. cDNA expression arrays bearing 588 known genes indicated that lesions express unexpectedly high levels of the early growth response gene, Egr-1 (NGFI-A), a zinc-finger transcription factor that modulates a cluster of stress-responsive genes including PDGF and TGF-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-inducible genes were also strongly elevated in the lesion. Time-course analyses revealed that Egr-1 was not induced ex vivo. Immunocytochemistry indicated 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 receptor-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 atherogenic factors may be a key step in coordinating the cellular events that result in vascular lesions.
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Cited by
Chiu, J.-J., & Chien, S. (2011) · Physiological Reviews · doi:10.1152/physrev.00047.2009 · Cited by 2,280
Fluid shear stress and the vascular endothelium: for better and for worse
Resnick, N., Yahav, H., Shay-Salit, A., Shushy, M., Schubert, S., Zilberman, L. C. M., & Wofovitz, E. (2003) · Progress in Biophysics and Molecular Biology · doi:10.1016/s0079-6107(02)00052-4 · Cited by 577
Shear Stress–Initiated Signaling and Its Regulation of Endothelial Function
Zhou, J., Li, Y.-S., & Chien, S. (2014) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.114.303422 · Cited by 561
Lee, C. G., Cho, S. J., Kang, M. J., Chapoval, S. P., Lee, P. J., Noble, P. W., Yehualaeshet, T., Lu, B., Flavell, R. A., Milbrandt, J., et al. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040104 · Cited by 369
Celis, J. E., Kruhøffer, M., Gromova, I., Frederiksen, C., Østergaard, M., Thykjaer, T., Gromov, P., Yu, J., Pálsdóttir, H., Magnusson, N., et al. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01771-3 · Cited by 314
Metadata
- Authors
- McCaffrey, T. A., Fu, C., Du, B., Eksinar, S., Kent, K. C., Bush, H., Kreiger, K., Rosengart, T., Cybulsky, M. I., Silverman, E. S., & Collins, T.
- Venue
- Journal of Clinical Investigation
- Published
- 2000-03-01
- Volume
- 105
- Issue
- 5
- Pages
- 653-662
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1993573575
- Cited by
- 294
- References
- 0
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- bronze
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- McCaffrey, T. A., Fu, C., Du, B., Eksinar, S., Kent, K. C., Bush, H., Kreiger, K., Rosengart, T., Cybulsky, M. I., Silverman, E. S., & Collins, T. (2000). High-level expression of Egr-1 and Egr-1–inducible genes in mouse and human atherosclerosis. Journal of Clinical Investigation. https://doi.org/10.1172/jci8592
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