This Article Full Text Full Text (PDF) All Versions of this Article: 94/3/333    most recent 01.RES.0000112405.61577.95v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Harja, E. Articles by Yan, S.-F. Search for Related Content PubMed PubMed Citation Articles by Harja, E. Articles by Yan, S.-F. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL Related Collections Mechanism of atherosclerosis/growth factors Other Vascular biology

(Circulation Research. 2004;94:333.)
© 2004 American Heart Association, Inc.

Molecular Medicine

Early Growth Response-1 Promotes Atherogenesis

Mice Deficient in Early Growth Response-1 and Apolipoprotein E Display Decreased Atherosclerosis and Vascular Inflammation

Evis Harja, Loredana G. Bucciarelli, Yan Lu, David M. Stern, Yu Shan Zou, Ann Marie Schmidt, Shi-Fang Yan

From the Division of Surgical Science, Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, NY.

Correspondence to Dr Shi-Fang Yan, BB1705, Department of Surgery, College of Physicians and Surgeons of Columbia University, 630 W 168th St, New York, NY 10032. E-mail sy18{at}columbia.edu

Early growth response-1 (Egr-1) regulates expression of proinflammatory and procoagulant genes in acute cell stress. Experimental evidence suggested that Egr-1 transcripts were upregulated in human atherosclerotic plaques versus adjacent unaffected tissue. To test the impact of Egr-1 in chronic vascular stress, we examined its role in a murine model of atherosclerosis. Real-time PCR analysis of aortae retrieved from apoE^-/- mice demonstrated increased Egr-1 transcripts in an age-dependent manner, compared with aortae retrieved from C57BL/6 control animals. Therefore, homozygous Egr-1^-/- mice were bred into the apoE^-/- background. Homozygous double-knockout mice (Egr-1^-/-/apoE^-/-) in the C57BL/6 background were maintained on normal chow diet. At age 14 and 24 weeks, atherosclerotic lesion area and complexity at the aortic root were strikingly decreased in mice deficient in both Egr-1 and apoE compared with mice deficient in apoE alone. In parallel, transcripts for genes regulating the inflammatory/prothrombotic response were diminished in Egr-1^-/-/apoE^-/- aortae versus apoE^-/-. In vitro, oxidized low-density lipoprotein (OxLDL), a key factor inciting atherogenic mechanisms in the vasculature, upregulated Egr-1 expression in monocytes via the MEK-ERK1/2 pathway. We conclude that Egr-1 broadly regulates expression of molecules critically linked to atherogenesis and lesion progression.

Key Words: transcription factor • oxidized low-density lipoprotein • signaling pathway • hypercholesterolemia • atherosclerosis

This article has been cited by other articles:

				H. Beck, M. Semisch, C. Culmsee, N. Plesnila, and A. K. Hatzopoulos Egr-1 Regulates Expression of the Glial Scar Component Phosphacan in Astrocytes after Experimental Stroke Am. J. Pathol., July 1, 2008; 173(1): 77 - 92. [Abstract] [Full Text] [PDF]

				W. Jiang, S. R. Hall, M. P.W. Moos, R. Y. Cao, S. Ishii, K. O. Ogunyankin, L. G. Melo, and C. D. Funk Endothelial Cysteinyl Leukotriene 2 Receptor Expression Mediates Myocardial Ischemia-Reperfusion Injury Am. J. Pathol., March 1, 2008; 172(3): 592 - 602. [Abstract] [Full Text] [PDF]

				R. N. Hasan and A. I. Schafer Hemin Upregulates Egr-1 Expression in Vascular Smooth Muscle Cells via Reactive Oxygen Species ERK-1/2 Elk-1 and NF-{kappa}B Circ. Res., January 4, 2008; 102(1): 42 - 50. [Abstract] [Full Text] [PDF]

				D. Onat, S. Jelic, A. M. Schmidt, J. Pile-Spellman, S. Homma, M. Padeletti, Z. Jin, T. H. Le Jemtel, P. C. Colombo, and L. Feng Vascular endothelial sampling and analysis of gene transcripts: a new quantitative approach to monitor vascular inflammation J Appl Physiol, November 1, 2007; 103(5): 1873 - 1878. [Abstract] [Full Text] [PDF]

				E. L. Kramer, G. H. Deutsch, M. A. Sartor, W. D. Hardie, M. Ikegami, T. R. Korfhagen, and T. D. Le Cras Perinatal increases in TGF-{alpha} disrupt the saccular phase of lung morphogenesis and cause remodeling: microarray analysis Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L314 - L327. [Abstract] [Full Text] [PDF]

				S.-F. Yan, E. Harja, M. Andrassy, T. Fujita, and A. M. Schmidt Protein Kinase C {beta}/Early Growth Response-1 Pathway: A Key Player in Ischemia, Atherosclerosis, and Restenosis J. Am. Coll. Cardiol., October 27, 2006; 48(9_Suppl_A): A47 - A55. [Abstract] [Full Text] [PDF]

				S.-J. Chen, H. Ning, W. Ishida, S. Sodin-Semrl, S. Takagawa, Y. Mori, and J. Varga The Early-Immediate Gene EGR-1 Is Induced by Transforming Growth Factor-beta and Mediates Stimulation of Collagen Gene Expression J. Biol. Chem., July 28, 2006; 281(30): 21183 - 21197. [Abstract] [Full Text] [PDF]

				K. Eto, V. Kaur, and M. K. Thomas Regulation of Insulin Gene Transcription by the Immediate-Early Growth Response Gene Egr-1 Endocrinology, June 1, 2006; 147(6): 2923 - 2935. [Abstract] [Full Text] [PDF]

				N. D. Kim, J.-O. Moon, A. L. Slitt, and B. L. Copple Early Growth Response Factor-1 Is Critical for Cholestatic Liver Injury Toxicol. Sci., April 1, 2006; 90(2): 586 - 595. [Abstract] [Full Text] [PDF]

				D. Bernhard, A. Rossmann, B. Henderson, M. Kind, A. Seubert, and G. Wick Increased Serum Cadmium and Strontium Levels in Young Smokers: Effects on Arterial Endothelial Cell Gene Transcription Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 833 - 838. [Abstract] [Full Text] [PDF]

				L. M. Khachigian Early Growth Response-1 in Cardiovascular Pathobiology Circ. Res., February 3, 2006; 98(2): 186 - 191. [Abstract] [Full Text] [PDF]

				A. Pandolfi, A. Solini, G. Pellegrini, G. Mincione, S. Di Silvestre, P. Chiozzi, A. Giardinelli, M. C. Di Marcantonio, A. Piccirelli, F. Capani, et al. Selective Insulin Resistance Affecting Nitric Oxide Release But Not Plasminogen Activator Inhibitor-1 Synthesis in Fibroblasts From Insulin-Resistant Individuals Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2392 - 2397. [Abstract] [Full Text] [PDF]

				M. Kamimura, C. Viedt, A. Dalpke, M. E. Rosenfeld, N. Mackman, D. M. Cohen, E. Blessing, M. Preusch, C. M. Weber, J. Kreuzer, et al. Interleukin-10 Suppresses Tissue Factor Expression in Lipopolysaccharide-Stimulated Macrophages via Inhibition of Egr-1 and a Serum Response Element/MEK-ERK1/2 Pathway Circ. Res., August 19, 2005; 97(4): 305 - 313. [Abstract] [Full Text] [PDF]

				J.-H. Kim, K. Yamaguchi, S.-H. Lee, P. K. Tithof, G. S. Sayler, J.-H. Yoon, and S. J. Baek Evaluation of Polycyclic Aromatic Hydrocarbons in the Activation of Early Growth Response-1 and Peroxisome Proliferator Activated Receptors Toxicol. Sci., May 1, 2005; 85(1): 585 - 593. [Abstract] [Full Text] [PDF]

				J. M. Martinez, S. J. Baek, D. M. Mays, P. K. Tithof, T. E. Eling, and N. J. Walker EGR1 Is a Novel Target for AhR Agonists in Human Lung Epithelial Cells Toxicol. Sci., December 1, 2004; 82(2): 429 - 435. [Abstract] [Full Text] [PDF]

				M. Kamimura, F. Bea, T. Akizawa, H. A. Katus, J. Kreuzer, and C. Viedt Platelet-Derived Growth Factor Induces Tissue Factor Expression in Vascular Smooth Muscle Cells via Activation of Egr-1 Hypertension, December 1, 2004; 44(6): 944 - 951. [Abstract] [Full Text] [PDF]

				S. Forrest and C. McNamara Id Family of Transcription Factors and Vascular Lesion Formation Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 2014 - 2020. [Abstract] [Full Text] [PDF]