Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation Research
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Circulation Research. 2006;98:186-191
doi: 10.1161/01.RES.0000200177.53882.c3
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Khachigian, L. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Khachigian, L. M.
Related Collections
Right arrow Restenosis
Right arrow Angiogenesis
Right arrow Pathophysiology
Right arrow Other Vascular biology
(Circulation Research. 2006;98:186.)
© 2006 American Heart Association, Inc.

MiniReview

Early Growth Response-1 in Cardiovascular Pathobiology

Levon M. Khachigian

From the Centre for Vascular Research, Department of Pathology, University of New South Wales, and Department of Haematology, The Prince of Wales Hospital, Sydney, Australia.

Correspondence to Levon M. Khachigian, PhD, DSc, Centre for Vascular Research, Department of Pathology, The University of New South Wales, Sydney NSW 2052, Australia. E-mail L.Khachigian{at}unsw.edu.au

Abstract

The immediate-early gene product and zinc finger transcription factor early growth response (Egr)-1 plays a key master regulatory role in multiple cardiovascular pathological processes. This article reviews the amassing recent evidence implicating Egr-1 in atherosclerosis, intimal thickening after acute vascular injury, ischemic pathology, angiogenesis, allograft rejection, and cardiac hypertrophy.


Key Words: Egr-1 • atherosclerosis • vascular injury • angiogenesis • ischemia and ischemia-reperfusion • allograft rejection • cardiac hypertrophy

Early growth response (Egr)-1,1 also known as NGFI-A,2 zif268,3 krox-24,4 and TIS85, is a transcription factor and product of an immediate-early gene located on human chromosome 5q23-q31 encoding 2 exons.1 The DNA binding domain of Egr-1 contains 3 zinc fingers of the Cys2-His2 subtype that bind preferentially to GC-rich elements.6 Egr-1 is poorly expressed in the normal artery wall but is activated by acute mechanical injury7 and other vascular stresses such as angiotensin II,8 lysophosphatidylcholine,9 PDGF,10 FGF-1,11 FGF-2,12 and fluid shear stress.13 Transcription of the Egr-1 gene is dependent on Ras-Raf-MEK-ERK1/2 pathway signaling (which is itself activated by acute vascular injury8,12,14,15) and serum-response elements in the Egr-1 promoter.16 These elements mediate Egr-1 inducibility in response to a variety of agonists, including thrombin,17 lipopolysaccharide,18 and hypoxia,19 and, as in the c-Fos promoter, involve interactions between ternary complex factors (TCF) and serum response factor (SRF).20 Recent studies suggest that nuclear accumulation of Egr-1 appears to require interaction of Gab1 (growth factor receptor-bound protein 2 [Grb2]-associated binder-1) with ERK1/2 via the proline-rich MET-binding domain in Gab1.21

Egr-1 is a master regulator because it controls the expression of a wide variety of genes. Oligonucleotide-based microarray analysis provided insights into the spectrum of these Egr-1–dependent genes. Expression of more than 300 genes was altered (229 upregulated, 74 downregulated) 3-fold or more 48 hours following human umbilical vein endothelial cell (HUVEC) infection with an adenovirus-driven form of Egr-1 resistant to transcriptional repression by its endogenous inhibitor NAB.22 These genes may broadly be grouped as transcription factors (eg, Egr-1, NAB1), signaling factors (eg, Notch3, Rad), growth factors and cytokines (eg, TGF-ß, CLF1), cell-cycle regulators (eg, cyclin D1, p57kip2, matrix proteins [eg, fibronectin, osteopontin]) and ion channel regulators (eg, Na+/Ca2+-exchanger).22

Egr-1–dependent gene expression involves functional cooperativity (positive and negative) between Egr-1 and a growing number of other transcription or regulatory factors including nuclear factor of activated T cells (NFAT),23,24 steroidogenic factor-1 (SF-1),25,26 AP-2 and the glucocorticoid receptor,27 p300,25 RelA (p65),28,29 p53,30 Sp131 as well as NAB (NAB132 and NAB233). It is therefore quite likely that Egr-1 does not act alone, but works in concert with other transcription factors. We described functional interplay between Egr-1 and Sp1 in the context of PDGF-A34 and PDGF-B7 promoters, now recognized as a more general regulatory circuit in inducible gene expression. Examples of other genes that may be controlled by Egr-1/Sp1 exchange include the HGF receptor,35 manganese superoxide dismutase,36 RET protooncogene,37 tissue factor,38 and 5-lipoxogenase.39

This article reviews the growing evidence implicating Egr-1 in the control of a wide variety of cardiovascular pathological processes (Figure).


Figure 1
View larger version (42K):
[in this window]
[in a new window]
  		Schematic depicting various cardiovascular pathological processes thought to be under transcriptional control of the inducible immediate-early gene product and zinc finger nuclear regulatory factor, Egr-1. Egr-1 is activated by multiple pathophysiological stimuli involving mitogen-activated protein kinases and SRE-dependent transcription. Egr-1, once induced, as a master regulator, controls effector genes implicated in a myriad of cardiovascular conditions such as lesion development, hypertrophy, ischemia, and angiogenesis. Egr-1 is but 1 of many transcription factors involved in these processes and its interactions with these other factors are yet to be delineated.

Atherosclerosis

Egr-1 contributes to the pathogenesis of atherosclerotic lesions. McCaffrey et al performed cDNA array and RT-PCR analysis comparing tissue from the dissected fibrous cap of human lesions with the underlying tunica media of patients with obstructive carotid atherosclerosis and revealed 5-fold higher levels of Egr-1 in lesions.40 Egr-1 was expressed mainly in {alpha}-SM-actin–positive cells in areas of macrophage infiltration, as well as in endothelial cells.40 Subsequent studies comparing Egr-1 protein expression in cells derived from the human atherosclerotic lesion and media at low passage revealed greater expression in lesions.41

Egr-1 is expressed in SMCs of atherosclerotic lesions in LDL receptor–deficient mice fed a high-fat diet for 5 weeks. Egr-1 staining intensity in lesions increased progressively by 10 and 20 weeks,40 observations supported by studies in apolipoprotein E (apoE)-null mice.42 Lesion area in mice deficient in both Egr-1 and apoE is dramatically reduced compared with mice lacking apoE alone. Female 24-week-old double-knockout mice fed a normal chow diet had 7-fold smaller lesions than apoE-null mice.42 Egr-1 is also found in inflammatory cells of vascular lesions. For example, Egr-1 is expressed in CD68+ macrophages of aortic atherosclerotic lesions in fructose-fed LDL receptor–deficient mice.43 In innominate arteries of apoE–/– mice, Egr-1 was primarily colocalized with macrophages in the lateral margins of advanced atherosclerotic lesions.44 Thus Egr-1 is found in several cell types within atherosclerotic lesions and is a factor required in atherogenesis. Egr-1 may also play a role in the pathophysiology of stenosed calcific valvular disease. Egr-1 has been detected in calcific human aortic valve cusps compared with noncalcified normal cusps.45

Egr-1 expression in lesions can be reduced with standard pharmacological agents. For example, simvastatin (50 mg/kg/d),a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, inhibits Egr-1 protein expression in lesions of apoE-null mice by more than 60%.44 This was accompanied by reduced tissue factor expression and fewer macrophages in the lesion.44 Chlamydia pneumoniae, a bacterium implicated in atherogenesis, can induce Egr-1 mRNA and protein expression in SMCs and macrophages within 1 hour apparently via ERK signaling.46,47 siRNA targeting human EGR-1 blocks C pneumoniae inducible DNA synthesis after 48 hours.46

Intimal Thickening After Acute Vascular Injury

Almost a decade ago we demonstrated by in situ hybridization that Egr-1 is rapidly (within hours) and transiently induced at the endothelial wound edge following balloon catheter scrape injury to the aortae of rats.7 In the same (endothelial denudation) model, we found that Egr-1 is expressed later by migrating SMCs.10 The expression and nuclear translocation of Egr-1 after mechanical injury is, at least in vitro, dependent on the release of endogenous FGF-2 and its paracrine activation of MEK/ERK-dependent signaling.12 FGF-2, a potent agonist of Egr-1, plays an important role vascular repair after injury. FGF-2 is locally and transiently (within minutes) released in the coronary arteries of humans undergoing stenting.48 SMC migration in rats after deendothelialization is augmented by systemic administration of FGF-2 and blocked by infusion of neutralizing antibodies to FGF-2.49

That Egr-1 plays a critical role as a mediator of SMC growth and intimal thickening in the reparative response to vascular injury has been demonstrated using a variety of synthetic nucleic acid-based gene-silencing approaches. For example, antisense oligonucleotides (15-mers) with phosphorothioate linkages targeting various regions in rat Egr-1 mRNA, unlike random, scrambled, sense or mismatch versions, blocked primary aortic SMC replication and regrowth after in vitro scraping injury.50 Catalytic 34-mer DNA molecules (DNAzyme ED5) which target and degrade rat Egr-1 mRNA, also inhibited SMC growth and repair in vitro and, when delivered adventitially to rat common carotid arteries, suppressed Egr-1 protein expression after 1 hour and intimal thickening 14 days after balloon angioplasty.51 ED5 also blocks neointima formation in rat carotid arteries 18 days after permanent ligation.52 The DNAzyme has since been used to suppress the development of other proliferative states. For example, ED5 reduces cortical Egr-1 mRNA expression and interstitial fibrosis in rats 7 days after renal obstruction (unilateral ureteral ligation) and delivery by electroporation. In this model, the DNAzyme inhibited TGF-ß, {alpha}-SM-actin and type I collagen mRNA expression.53

DNAzymes targeting the human version of Egr-1, which also inhibit Egr-1 expression and proliferation of human and porcine aortic SMCs, reduce in-stent restenosis in pig coronary arteries 30 days after endoluminal delivery at the time of stenting.54 We have recently reported that the inhibitory potency of DNAzymes in SMCs can be improved by the incorporation of certain structural modifications such as locked nucleic acids (LNA).55 Ohtani et al demonstrated that intraluminal delivery of double-stranded cis-element oligonucleotide "decoys" bearing Egr-1 binding sites inhibit the expression of Egr-1–dependent genes, such as PDGF-B, TGF-ß, and MCP-1, and block intimal hyperplasia 7 and 28 days, respectively, after balloon injury to the carotid arteries of hypercholesterolemic rabbits.56 It is presently unknown whether injury-inducible intimal thickening is compromised in Egr-1–null mice. Thus, antisense, DNAzyme and decoy approaches targeting Egr-1, which is rapidly upregulated by acute injury, may be useful as antigene strategies in vascular occlusive disorders. Blockade of neointima formation by targeting other transcription factors, such as NFAT,57 STAT3,58 nuclear factor {kappa}B,59 and c-Jun,60 that are also activated by arterial injury57,58,60,61 suggests that the possibility of compound inhibition of postangioplasty restenosis in strategies targeting multiple factors.

Hypoxia and Ischemia

Understanding transcriptional changes in the brain after ischemia may provide therapeutic molecular targets for the treatment of stroke, a consequence of atherosclerosis. Several lines of evidence identify Egr-1 as a hypoxia-inducible factor. Gubits et al showed that unilateral ligation of the common carotid artery in 7-day-old pup rats followed by 3 hours of hypoxia (8% O2) results in increased Egr-1 mRNA expression in the ipsilateral forebrain within a few hours.62 DNA microarray studies later demonstrated that Egr-1 is upregulated in the hippocampal CA1 sector in rats 2 minutes after global cerebral ischemia.63 Finally, Egr-1 and Egr-1–dependent genes (such as PAI-1, ICAM-1, IL-1ß, and MIP-1) are induced in the periinfarction cortex of adult rats 24 hours after permanent middle cerebral artery occlusion.64 Egr-1 is also upregulated in the kidney in response to renal artery occlusion.65,66

Egr-1 appears to be involved in the pathogenesis of ischemic lung tissue damage. In a mouse model of lung ischemia and ischemia-reperfusion, Egr-1 (but not Sp1) was induced 3-fold within 15 minutes and approximately 10-fold after 1 hour, then induced 20-fold after 3 hours of reperfusion.67 That Egr-1–deficient mice display increased survival and lung function after pulmonary ischemia-reperfusion demonstrates a causal relationship between Egr-1 and ischemia-reperfusion damage.67 Egr-1–deficient animals had lower expression of genes such as tissue factor, PAI-1, and ICAM-1, suggesting Egr-1 governance of procoagulant and proinflammatory genes during ischemia-reperfusion injury. Recent studies show that Egr-1 expression, ERK, and JNK phosphorylation after lung ischemia-reperfusion is reduced in PKC-ß knockout mice or wild-type mice fed the PKC-ß inhibitor ruboxistaurin,68 demonstrating the importance of this PKC isoform in Egr-1 signaling. Hypoxia induces Egr-1 expression in endothelial cells via the PKC-{alpha}–mediated Ras/Raf-1/ERK1/2 pathway.69

cDNA array analysis further showed that Egr-1 mRNA levels in rat lungs increase 5-fold 1 hour after warm ischemia following surgical extirpation compared with controls.70 Chronic exposure (14 days) of newborn calves to 12%, rather than 21%, O2 upregulates Egr-1 protein expression in pulmonary artery adventitial fibroblasts. Hypoxia (1%) induces Egr-1 expression and DNA synthesis in fibroblasts cultured from hypoxic animals, after 6 and 24 hours, respectively. Hypoxia-inducible fibroblast proliferation, cyclin D, and epidermal growth factor receptor expression is inhibited after 48 hours.71 Interestingly, Egr-1 mRNA is increased 2-fold in the lung and 6-fold in the rat heart 6 hours following exposure to 0.1% carbon monoxide.72 Egr-1 is activated in response to cardiac ischemia. For example, Egr-1 mRNA is expressed after cardioplegic arrest and reperfusion in human hearts and in rat hearts subjected to cold cardioplegia for 40 minutes followed by 40 minutes of reperfusion.73 Egr-1 expression is thus regulated by ischemic and ischemic-reperfusive stress in multiple cell and tissue types.

Cardiac Hypertrophy

A role for Egr-1 in cardiac hypertrophy was suggested by the capacity of norepinephrine and phenylephrine to stimulate Egr-1 in rat hearts.74 Recently, Buitrago et al75 demonstrated that NAB1 and Egr-1 serve as endogenous regulators of pathologic cardiac hypertrophy. Left ventricular myocardial NAB1 expression increased in ß1-adrenergic receptor transgenic mice, a well-established model of heart failure. Adenovirus-driven NAB1 suppressed cardiomyocyte hypertrophy, skeletal organization, and protein synthesis, whereas cardiomyocyte growth was unaffected by a mutant form of NAB1 that lacked the Egr-binding site. Although adrenergic stimulation led to ventricular hypertrophy in wild-type mice, this was significantly reduced in NAB1-overexpressing mice. Complementing these observations, ventricular and cardiomyocyte hypertrophy were reduced in Egr-1–null mice subjected to transverse aortic constriction-induced pressure overload. In contrast, physiologic hypertrophy induced by exercise was unaffected in NAB1 transgenic mice compared with wild-type animals, suggesting a role in pathological but not physiological hypertrophy.75 Saadane et al by contrast showed no change in total ventricular weight in Egr-1–deficient mice after chronic infusion of isoproterenol/phenylephrine compared with wild type mice, despite dramatic differences in adrenoreceptor-stimulated expression of genes such as GATA-4 and Nkx2.5.76

Allograft Rejection

Egr-1 also appears to play a role in cardiac allograft rejection. Egr-1 mRNA and protein were detected in leukocytes and cardiac myocytes of grade 3 endomyocardial biopsies but not in grade 0 biopsies. Egr-1 is expressed in the coronaries of patients with coronary artery vasculopathy (CAV).77 These findings are supported by observations of Egr-1 expression in SMCs of rejected cardiac allografts in monkeys undergoing heterotopic abdominal heart transplants.78 Egr-1 and Egr-1–dependent genes, such as ICAM-1, VCAM-1, and PDGF-A, are induced following transplantation of heterotopic murine cardiac allografts. In contrast, these genes are poorly expressed in homozygous Egr-1–deficient donor allografts, in which parenchymal rejection and CAV are suppressed.79 Antisense Egr-1 oligonucleotides delivered at the time of organ harvest inhibit Egr-1 expression and the development of CAV.79 Antisense Egr-1 also block lung transplant leukostasis, inflammation, and thrombosis in rats together with improved graft function and recipient survival.80 These findings thus implicate Egr-1 in vasculopathy and organ rejection.

Angiogenesis

Inducible expression of Egr-1 in activated vascular endothelium7 led us to investigate whether Egr-1 may play direct a role in the angiogenic process. Observations of poor neovascularization in subcutaneous Matrigel implants of Egr-1–deficient mice were consistent with suppressed implant angiogenesis in normal mice using Egr-1 DNAzymes. These agents inhibited microvascular endothelial cell proliferation and migration and microtubule network formation in vitro, blocked VEGF-inducible corneal neovascularization in rats, and reduced tumor growth and tumor angiogenesis in mice.81 These findings are complemented by investigations using NAB2. NAB2, but not a dominant-negative form, abrogates tubule formation in culture.82 Additionally, adenovirus-driven NAB2 reduces in vitro tubule and sprout formation and decreases plug neovascularization in mice.83 How Egr-1 controls angiogenesis is presently unclear, but is likely to involve its orchestration of multiple growth mediators and receptors. For example, Egr-1 controls the expression of FGF-2,81 Flt-1,84 tissue factor,83 and uPA83 in the context of angiogenesis. Recent studies indicate that Egr-1 controls CCN1, an angiogenic factor produced by SMCs that promotes cell adhesion, replication and differentiation.85 Thus, Egr-1, like HIF86 is an inducible proangiogenic gene regulatory factor.

Concluding Remarks

Egr-1 is a master regulator that plays a key role in a variety of cardiovascular pathological processes such as atherosclerosis, intimal thickening following acute vascular injury, ischemia-reperfusion, cardiac hypertrophy, allograft rejection, and angiogenesis. Much of this knowledge has been derived from investigations using Egr-1–null mice or specific molecular suppressors of Egr-1, such as antisense oligonucleotides, decoys, siRNA, DNAzymes, or NABs. Egr-1 dynamically links changes in the local cellular environment with the altered expression of key genes mediating a broad spectrum of vascular pathologies. Egr-1 transcriptional activity involves functionally important interactions with NABs and other regulators, although this knowledge is still relatively limited. The influence of oxidation, phosphorylation, acetylation, and deacetylation on Egr-1 transactivation and the specific disease contexts involved are also not clear. Future studies should address these deficiencies and extend the key pathophysiological roles of Egr-1 beyond rodent models, from where much of our current understanding on Egr-1 is largely derived, to larger animal systems. This will help direct which of the panoply of cardiovascular conditions possibly regulated by Egr-1 in humans could be targeted with Egr-1–specific strategies as primary or adjunctive therapies.

Acknowledgments

The author thanks Dr Ravinay Bhindi and Gabriella Khachigian for helpful comments. Work in the laboratory of the author was supported by grants from the National Health and Medical Research Council, National Heart Foundation, Australian Research Council, and the New South Wales State Department of Health. The author is a Senior Principal Research Fellow of the National Health and Medical Research Council.

Footnotes

Intellectual property on Egr-1 is owned by Unisearch/NewSouth Innovations Ltd, an entity of The University of New South Wales.

Original received September 10, 2005; revision received October 27, 2005; accepted December 1, 2005.

References

  1. Sukhatme VP, Cao X, Chang LL, Tsai-Morris C-H, Stamenkovich D, Ferreira PCP, Cohen DR, Edwards SA, Shows TB, Curran T, Le Beau MM, Adamson ED. A zinc-finger encoding gene corregulated with c-Fos during growth and differentiation and after depolarization. Cell. 1988; 53: 37–43.[CrossRef][Medline] [Order article via Infotrieve]
  2. Milbrandt J. A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor. Science. 1987; 238: 797–799.[Abstract/Free Full Text]
  3. Lau LF, Nathans D. Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc. Proc Natl Acad Sci U S A. 1987; 84: 1182–1186.[Abstract/Free Full Text]
  4. Lemaire P, Revelant O, Bravo R, Charnay P. Two mouse genes encoding potential transcription factors with identical DNA-binding domains are activated by growth factors in cultured cells. Proc Natl Acad Sci U S A. 1988; 85: 4691–4695.[Abstract/Free Full Text]
  5. Lim RW, Varnum BC, Herschman HR. Cloning of tetradecanoyl phorbol ester-induced ‘primary response’ sequences and their expression in density-arrested Swiss 3T3 cells and a TPA nonproliferative variant. Oncogene. 1987; 1: 263–270.[Medline] [Order article via Infotrieve]
  6. Gashler A, Sukhatme V. Early growth response protein 1 (Egr-1): prototype of a zinc-finger family of transcription factors. Prog Nucl Acid Res. 1995; 50: 191–224.
  7. Khachigian LM, Lindner V, Williams AJ, Collins T. Egr-1-induced endothelial gene expression: a common theme in vascular injury. Science. 1996; 271: 1427–1431.[Abstract]
  8. Day FL, Rafty LA, Chesterman CN, Khachigian LM. Angiotensin II (ATII)-inducible platelet-derived growth factor A-chain gene expression is p42/44 extracellular signal-regulated kinase-1/2 and Egr-1 dependent and modulated via the ATII type 1 but not type 2 receptor - induction by ATII antagonized by nitric oxide. J Biol Chem. 1999; 274: 23726–23733.[Abstract/Free Full Text]
  9. Morimoto M, Kume N, Miyamoto S, Ueno Y, Kataoka H, Minami M, Hayashida K, Hashimoto N, Kita T. Lysophosphatidylcholine induces early growth response factor-1 expression and activates the core promoter of PDGF-A chain in vascular endothelial cells. Arterioscler Thromb Vasc Biol. 2001; 21: 771–776.[Abstract/Free Full Text]
  10. Silverman ES, Khachigian LM, Lindner V, Williams AJ, Collins T. Inducible PDGF A-chain transcription in vascular smooth muscle cells is mediated by Egr-1 displacement of Sp1 and Sp3. Am J Physiol. 1997; 42: H1415–H1426.
  11. Delbridge GJ, Khachigian LM. FGF-1-induced PDGF A-chain gene expression in vascular endothelial cells involves transcriptional activation by Egr-1. Circ Res. 1997; 81: 282–288.[Abstract/Free Full Text]
  12. Santiago FS, Lowe HC, Day FL, Chesterman CN, Khachigian LM. Early growth response factor-1 induction by injury is triggered by release and paracrine activation by fibroblast growth factor-2. Am J Pathol. 1999; 154: 937–944.[Abstract/Free Full Text]
  13. Khachigian LM, Anderson KA, Halnon NJ, Resnick N, Gimbrone MA Jr, Collins T. Egr-1 is activated in endothelial cells exposed to fluid shear stress and interacts with a novel shear-stress response element in the PDGF A-chain promoter. Arterioscl Thromb Vasc Biol. 1997; 17: 2280–2286.[Abstract/Free Full Text]
  14. Pyles JM, March KL, Franklin M, Mehdi K, Wilensky RL, Adam LP. Activation of MAP kinase in vivo follows balloon overstretch injury of porcine coronary and carotid arteries. Circ Res. 1997; 81: 904–910.[Abstract/Free Full Text]
  15. Hu Y, Cheng L, Hochleitner B-W, Xu Q. Activation of mitogen-activated protein kinases (ERK/JNK) and AP-1 transcription factor in rat carotid arteries after balloon injury. Arterioscler Thromb Vasc Biol. 1997; 17: 2808–2816.[Abstract/Free Full Text]
  16. Sakamoto KM, Bardeleben C, Yates KE, Raines MA, Golde DW, Gasson JC. 5' upstream sequence and genomic structure of the human primary response gene, EGR-1/TIS-8. Oncogene. 1991; 6: 867–871.[Medline] [Order article via Infotrieve]
  17. Wu SQ, Minami T, Donovan DJ, Aird WC. The proximal serum response element in the Egr-1 promoter mediates response to thrombin in primary human endothelial cells. Blood. 2002; 100: 4454–4461.[Abstract/Free Full Text]
  18. Guha M, O’Connell MA, Pawlinski R, Hollis A, McGovern P, Yan SF, Stern D, Mackman N. Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor alpha expression by inducing Elk-1 phosphorylation and Egr-1 expression. Blood. 2001; 98: 1429–1439.[Abstract/Free Full Text]
  19. Yan SF, Lu J, Zou YS, Soh-Won J, Cohen DM, Buttrick PM, Cooper DR, Steinberg SF, Mackman N, Pinsky DJ, Stern DM. Hypoxia-associated induction of early growth response-1 gene expression. J Biol Chem. 1999; 274: 15030–15040.[Abstract/Free Full Text]
  20. Buchwalter G, Gross C, Wasylyk B. Ets ternary complex transcription factors. Gene. 2004; 324: 1–14.[CrossRef][Medline] [Order article via Infotrieve]
  21. Osawa M, Itoh S, Ohta S, Huang Q, Berk BC, Marmarosh NL, Che W, Ding B, Yan C, Abe J. ERK1/2 associates with the c-Met-binding domain of growth factor receptor-bound protein 2 (Grb2)-associated binder-1 (Gab1): role in ERK1/2 and early growth response factor-1 (Egr-1) nuclear accumulation. J Biol Chem. 2004; 279: 29691–29699.[Abstract/Free Full Text]
  22. Fu M, Zhu X, Zhang J, Liang J, Lin Y, Zhao L, Ehrengruber MU, Chen YE. Egr-1 target genes in human endothelial cells identified by microarray analysis. Gene. 2003; 315: 33–41.[CrossRef][Medline] [Order article via Infotrieve]
  23. Decker EL, Nehmann N, Kampen E, Eibel H, Zipfel PF, Skerka C. Early growth response proteins (EGR) and nuclear factors of activated T cells (NFAT) form heterodimers and regulate proinflammatory cytokine gene expression. Nucleic Acids Res. 2003; 31: 911–921.[Abstract/Free Full Text]
  24. Decker EL, Skerka C, Zipfel PF. The early growth response protein (EGR-1) regulates interleukin-2 transcription by synergistic interaction with the nuclear factor of activated T cells. J Biol Chem. 1998; 273: 26923–26930.[Abstract/Free Full Text]
  25. Mouillet JF, Sonnenberg-Hirche C, Yan X, Sadovsky Y. p300 regulates the synergy of steroidogenic factor-1 and early growth response-1 in activating luteinizing hormone-beta subunit gene. J Biol Chem. 2004; 279: 7832–7839.[Abstract/Free Full Text]
  26. Lee SL, Sadovsky Y, Swirnoff AH, Polish JA, Goda P, Gavrilina G, Milbrandt J. Luteinizing hormone deficiency and female infertility in mice lacking the transcription factor NGF-IA (Egr-1). Science. 1996; 273: 1219–1221.[Abstract]
  27. Wong DL, Siddall BJ, Ebert SN, Bell RA, Her S. Phenylethanolamine N-methyltransferase gene expression: synergistic activation by Egr-1, AP-2 and the glucocorticoid receptor. Brain Res Mol Brain Res. 1998; 61: 154–161.[Medline] [Order article via Infotrieve]
  28. Chapman NR, Perkins ND. Inhibition of the RelA(p65) NF-kappaB subunit by Egr-1. J Biol Chem. 2000; 275: 4719–4725.[Abstract/Free Full Text]
  29. Cogswell PC, Mayo MW, Baldwin AS Jr. Involvement of Egr-1/RelA synergy in distinguishing T cell activation from tumor necrosis factor-alpha-induced NF-kappa B1 transcription. J Exp Med. 1997; 185: 491–497.[Abstract/Free Full Text]
  30. Liu J, Grogan L, Nau MM, Allegra CJ, Chu E, Wright JJ. Physical interaction between p53 and primary response gene Egr-1. Int J Oncol. 2001; 18: 863–870.[Medline] [Order article via Infotrieve]
  31. Srivastava S, Weitzmann MN, Kimble RB, Rizzo M, Zahner M, Milbrandt J, Ross FP, Pacifici R. Estrogen blocks M-CSF gene expression and osteoclast formation by regulating phosphorylation of Egr-1 and its interaction with Sp-1. J Clin Invest. 1998; 102: 1850–1859.[Medline] [Order article via Infotrieve]
  32. Russo MW, Sevetson BR, Milbrandt J. Identification of NAB-1, a repressor of NGFI-A- and Krox20-mediated transcription. Proc Natl Acad Sci U S A. 1995; 92: 6873–6877.[Abstract/Free Full Text]
  33. Svaren J, Sevetson BR, Apel ED, Zimonjic DB, Popescu NC, Milbrandt J. NAB2, a corepressor of NGFI-A (Egr-1) and Krox20, is induced by proliferative and differentiative stimuli. Mol Cell Biol. 1996; 16: 3545–3553.[Abstract]
  34. Khachigian LM, Williams AJ, Collins T. Interplay of Sp1 and Egr-1 in the proximal PDGF-A promoter in cultured vascular endothelial cells. J Biol Chem. 1995; 270: 27679–27686.[Abstract/Free Full Text]
  35. Zhang X, Liu Y. Suppression of HGF receptor gene expression by oxidative stress is mediated through the interplay between Sp1 and Egr-1. Am J Physiol Renal Physiol. 2003; 284: F1216–F1225.[Abstract/Free Full Text]
  36. Maehara K, Uekawa N, Isobe K. Effects of histone acetylation on transcriptional regulation of manganese superoxide dismutase gene. Biochem Biophys Res Commun. 2002; 295: 187–192.[CrossRef][Medline] [Order article via Infotrieve]
  37. Andrew SD, Capes-Davis A, Delhanty PJ, Marsh DJ, Mulligan LM, Robinson BG. Transcriptional repression of the RET proto-oncogene by a mitogen activated protein kinase-dependent signalling pathway. Gene. 2002; 298: 9–19.[CrossRef][Medline] [Order article via Infotrieve]
  38. Mechtcheriskova D, Wlachos A, Holzmuller H, Binder BR. Vascular endothelial cell growth factor-induced tissue factor expression in endothelial cells is mediated by EGR-1. Blood. 1999; 93: 3811–3823.[Abstract/Free Full Text]
  39. Silverman ES, Du J, De Sanctis GT, Radmark O, Samuelsson B, Drazen JM, Collins T. Egr-1 and Sp1 interact functionally with the 5-lipoxygenase promoter and its naturally occurring mutants. Am J Respir Cell Mol Biol. 1998; 19: 316–323.[Abstract/Free Full Text]
  40. McCaffrey TA, Fu C, Du C, Eskinar S, Kent KC, Bush H Jr, Kreiger K, Rosengart T, Cybulsky MI, Silverman ES, Collins T. High-level expression of Egr-1 and Egr-1-inducible genes in mouse and human atherosclerosis. J Clin Invest. 2000; 105: 653–662.[Medline] [Order article via Infotrieve]
  41. Du B, Fu C, Kent KC, Bush H, Schulick AH, Kreiger K, Collins T, McCaffrey TA. Elevated Egr-1 in human atherosclerotic cells transcriptionally represses the transforming growth factor-b type II receptor. J Biol Chem. 2000; 275: 39039–39047.[Abstract/Free Full Text]
  42. Harja E, Bucciarelli LG, Lu Y, Stern DM, Zou YS, Schmidt AM, Yan SF. Early growth response-1 promotes atherogenesis: mice deficient in early growth response-1 and apolipoprotein E display decreased atherosclerosis and vascular inflammation. Circ Res. 2004; 94: 333–339.[Abstract/Free Full Text]
  43. Goetze S, Kintscher U, Kaneshiro K, Meehan WP, Collins A, Fleck E, Hsueh WA, Law RE. TNFalpha induces expression of transcription factors c-fos, Egr-1, and Ets-1 in vascular lesions through extracellular signal-regulated kinases 1/2. Atherosclerosis. 2001; 159: 93–101.[CrossRef][Medline] [Order article via Infotrieve]
  44. Bea F, Blessing E, Shelley MI, Shultz JM, Rosenfeld ME. Simvastatin inhibits expression of tissue factor in advanced atherosclerotic lesions of apolipoprotein E deficient mice independently of lipid lowering: potential role of simvastatin-mediated inhibition of Egr-1 expression and activation. Atherosclerosis. 2003; 167: 187–194.[CrossRef][Medline] [Order article via Infotrieve]
  45. Ghazvini-Boroujerdi M, Clark J, Narula N, Palmatory E, Connolly JM, DeFelice S, Xu J, Jian B, Hazelwood S, Levy RJ. Transcription factor Egr-1 in calcific aortic valve disease. J Heart Valve Dis. 2004; 13: 894–903.[Medline] [Order article via Infotrieve]
  46. Rupp J, Hellwig-Burgel T, Wobbe V, Seitzer U, Brandt E, Maass M. Chlamydia pneumoniae infection promotes a proliferative phenotype in the vasculature through Egr-1 activation in vitro and in vivo. Proc Natl Acad Sci U S A. 2005; 102: 3447–3452.[Abstract/Free Full Text]
  47. Bea F, Puolakkainen MH, McMillen T, Hudson FN, Mackman N, Kuo CC, Campbell LA, Rosenfeld ME. Chlamydia pneumoniae induces tissue factor expression in mouse macrophages via activation of Egr-1 and the MEK-ERK1/2 pathway. Circ Res. 2003; 92: 394–401.[Abstract/Free Full Text]
  48. Lowe HC, Chesterman CN, Hopkins A, Juergens CP, Khachigian LM. Acute local release of fibroblast growth factor-2 but not transforming growth factor-beta1 following coronary stenting. Thromb Haemost. 2001; 85: 574–576.[Medline] [Order article via Infotrieve]
  49. Jackson CL, Reidy MA. Basic fibroblast growth factor: its role in the control of smooth muscle cell migration. Am J Pathol. 1993; 143: 1024–1031.[Abstract]
  50. Santiago FS, Atkins DA, Khachigian LM. Vascular smooth muscle cell proliferation and regrowth after injury in vitro is dependent upon NGFI-A/Egr-1. Am J Pathol. 1999; 155: 897–905.[Abstract/Free Full Text]
  51. Santiago FS, Lowe HC, Kavurma MM, Chesterman CN, Baker A, Atkins DG, Khachigian LM. New DNA enzyme targeting Egr-1 mRNA inhibits vascular smooth muscle proliferation and regrowth factor injury. Nat Med. 1999; 5: 1264–1269.[CrossRef][Medline] [Order article via Infotrieve]
  52. Lowe HC, Chesterman CN, Khachigian LM. Catalytic antisense DNA molecules targeting Egr-1 inhibit neointima formation following permanent ligation of rat common carotid arteries. Thromb Haemost. 2002; 87: 134–140.[Medline] [Order article via Infotrieve]
  53. Nakamura H, Isaka Y, Tsujie M, Rupprecht HD, Akagi Y, Ueda N, Imai E, Hori M. Introduction of DNA enzyme for Egr-1 into tubulointerstitial fibroblasts by electroporation reduced interstitial alpha-smooth muscle actin expression and fibrosis in unilateral ureteral obstruction (UUO) rats. Gene Ther. 2002; 9: 495–502.[CrossRef][Medline] [Order article via Infotrieve]
  54. Lowe HC, Fahmy RG, Kavurma MM, Baker A, Chesterman CN, Khachigian LM. Catalytic oligodeoxynucleotides define a key regulatory role for early growth response factor-1 in the porcine model of coronary in-stent restenosis. Circ Res. 2001; 89: 670–677.[Abstract/Free Full Text]
  55. Fahmy RG, Khachigian LM. Locked nucleic acid-modified DNA enzymes targeting early growth response-1 inhibit vascular smooth muscle cell growth. Nucleic Acids Res. 2004; 32: 2281–2285.[Abstract/Free Full Text]
  56. Ohtani K, Egashira K, Usui M, Ishibashi M, Hiasa KI, Zhao Q, Aoki M, Kaneda Y, Morishita R, Takeshita A. Inhibition of neointimal hyperplasia after balloon injury by cis-element ‘decoy’ of early growth response gene-1 in hypercholesterolemic rabbits. Gene Ther. 2004; 11: 126–132.[CrossRef][Medline] [Order article via Infotrieve]
  57. Liu Z, Zhang C, Dronadula N, Li Q, Rao GN. Blockade of nuclear factor of activated T cells activation signaling suppresses balloon injury-induced neointima formation in a rat carotid artery model. J Biol Chem. 2005; 280: 14700–14708.[Abstract/Free Full Text]
  58. Shibata R, Kai H, Seki Y, Kato S, Wada Y, Hanakawa Y, Hashimoto K, Yoshimura A, Imaizumi T. Inhibition of STAT3 prevents neointima formation by inhibiting proliferation and promoting apoptosis of neointimal smooth muscle cells. Hum Gene Ther. 2003; 14: 601–610.[CrossRef][Medline] [Order article via Infotrieve]
  59. Landry DB, Couper LL, Bryant SR, Lindner V. Activation of the NF-kappa B and I kappa B system in smooth muscle cells after rat arterial injury. Induction of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1. Am J Pathol. 1997; 151: 1085–1095.[Abstract]
  60. Khachigian LM, Fahmy RG, Zhang G, Bobryshev YV, Kaniaros A. c-Jun regulates vascular smooth muscle cell growth and neointima formation after arterial injury: inhibition by a novel DNAzyme targeting c-Jun. J Biol Chem. 2002; 277: 22985–22991.[Abstract/Free Full Text]
  61. Autieri MV, Yue T-L, Ferstein GZ, Ohlstein E. Antisense oligonucleotides to the p65 subunit of NF-kB inhibit human vascular smooth muscle cell adherence and proliferation and prevent neointima formation in rat carotid arteries. Biochem Biophys Res Commun. 1995; 213: 827–836.[CrossRef][Medline] [Order article via Infotrieve]
  62. Gubits RM, Burke RE, Casey-McIntosh G, Bandele A, Munell F. Immediate early gene induction after neonatal hypoxia-ischemia. Brain Res Mol Brain Res. 1993; 18: 228–238.[Medline] [Order article via Infotrieve]
  63. Kawahara N, Wang Y, Mukasa A, Furuya K, Shimizu T, Hamakubo T, Aburatani H, Kodama T, Kirino T. Genome-wide gene expression analysis for induced ischemic tolerance and delayed neuronal death following transient global ischemia in rats. J Cereb Blood Flow Metab. 2004; 24: 212–223.[CrossRef][Medline] [Order article via Infotrieve]
  64. Lu P, Nakamoto Y, Nemoto-Sasaki Y, Fujii C, Wang H, Hashii M, Ohmoto Y, Kaneko S, Kobayashi K, Mukaida N. Potential interaction between CCR1 and its ligand, CCL3, induced by endogenously produced interleukin-1 in human hepatomas. Am J Pathol. 2003; 162: 1249–1258.[Abstract/Free Full Text]
  65. Ouellette AJ, Malt RA, Sukhatme VP, Bonventre JV. Expression of two "immediate early" genes, Egr-1 and c-fos, in response to renal ischemia and during compensatory renal hypertrophy in mice. J Clin Invest. 1990; 85: 766–771.[Medline] [Order article via Infotrieve]
  66. Heiniger CD, Kostadinova RM, Rochat MK, Serra A, Ferrari P, Dick B, Frey BM, Frey FJ. Hypoxia causes down-regulation of 11 beta-hydroxysteroid dehydrogenase type 2 by induction of Egr-1. FASEB J. 2003; 17: 917–919.[Abstract/Free Full Text]
  67. Yan SF, Fujita T, Lu J, Okada K, Shan Zou Y, Mackman N, Pinsky DJ, Stern DM. Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress. Nat Med. 2000; 6: 1355–1361.[CrossRef][Medline] [Order article via Infotrieve]
  68. Fujita T, Asai T, Andrassy M, Stern DM, Pinsky DJ, Zou YS, Okada M, Naka Y, Schmidt AM, Yan SF. PKCbeta regulates ischemia/reperfusion injury in the lung. J Clin Invest. 2004; 113: 1615–1623.[CrossRef][Medline] [Order article via Infotrieve]
  69. Lo LW, Cheng JJ, Chiu JJ, Wung BS, Liu YC, Wang DL. Endothelial exposure to hypoxia induces Egr-1 expression involving PKCalpha-mediated Ras/Raf-1/ERK1/2 pathway. J Cell Physiol. 2001; 188: 304–312.[CrossRef][Medline] [Order article via Infotrieve]
  70. Miyatake Y, Ikeda H, Michimata R, Koizumi S, Ishizu A, Nishimura N, Yoshiki T. Differential modulation of gene expression among rat tissues with warm ischemia. Exp Mol Pathol. 2004; 77: 222–230.[CrossRef][Medline] [Order article via Infotrieve]
  71. Banks MF, Gerasimovskaya EV, Tucker DA, Frid MG, Carpenter TC, Stenmark KR. Egr-1 antisense oligonucleotides inhibit hypoxia-induced proliferation of pulmonary artery adventitial fibroblasts. J Appl Physiol. 2005; 98: 732–738.[Abstract/Free Full Text]
  72. Gess B, Wolf K, Pfeifer M, Riegger GA, Kurtz A. In vivo carbon monoxide exposure and hypoxic hypoxia stimulate immediate early gene expression. Pflugers Arch. 1997; 434: 568–574.[CrossRef][Medline] [Order article via Infotrieve]
  73. Aebert H, Cornelius T, Ehr T, Holmer SR, Birnbaum DE, Riegger GA, Schunkert H. Expression of immediate early genes after cardioplegic arrest and reperfusion. Ann Thorac Surg. 1997; 63: 1669–1675.[Abstract/Free Full Text]
  74. Brand T, Sharma HS, Schaper W. Expression of nuclear proto-oncogenes in isoproterenol-induced cardiac hypertrophy. J Mol Cell Cardiol. 1993; 25: 1325–1337.[CrossRef][Medline] [Order article via Infotrieve]
  75. Buitrago M, Lorenz K, Maass M, Oberdorf-Maass S, Keller U, Schmitteckert EM, Ivaschenko Y, Lohse MJ, Engelhardt S. The transcriptional repressor NAB1 is a specific regulator of pathological cardiac hypertrophy. Nat Med. 2005; 11: 837–844.[CrossRef][Medline] [Order article via Infotrieve]
  76. Saadane N, Alpert L, Chalifour LE. Altered molecular response to adrenoreceptor-induced cardiac hypertrophy in Egr-1-deficient mice. Am J Physiol Heart Circ Physiol. 2000; 278: H796–H805.[Abstract/Free Full Text]
  77. Autieri MV, Kelemen SE, Gaughan JP, Eisen HJ. Early growth responsive gene (Egr)-1 expression correlates with cardiac allograft rejection. Transplantation. 2004; 78: 107–111.[Medline] [Order article via Infotrieve]
  78. Wada Y, Suzuki J, Kawauchi M, Kurabayashi M, Tsukioka K, Zhang T, Endoh M, Takayama K, Nagai R, Takamoto S, Isobe M, Amano J. Early growth-response factor 1 and basic transcriptional element-binding protein 2 expression in cardiac allografts. J Heart Lung Transplant. 2001; 20: 590–594.[CrossRef][Medline] [Order article via Infotrieve]
  79. Okada M, Wang CY, Hwang DW, Sakaguchi T, Olson KE, Yoshikawa Y, Minamoto K, Mazer SP, Yan SF, Pinsky DJ. Transcriptional control of cardiac allograft vasculopathy by early growth response gene-1 (Egr-1). Circ Res. 2002; 91: 135–142.[Abstract/Free Full Text]
  80. Okada M, Fujita T, Sakaguchi T, Olson KE, Collins T, Stern DM, Yan SF, Pinsky DJ. Extinguishing Egr-1-dependent inflammatory and thrombotic cascades after lung transplantation. FASEB J. 2001; 15: 2757–2759.[Free Full Text]
  81. Fahmy RG, Dass CR, Sun LQ, Chesterman CN, Khachigian LM. Transcription factor Egr-1 supports FGF-dependent angiogenesis during neovascularization and tumor growth. Nat Med. 2003; 9: 1026–1032.[CrossRef][Medline] [Order article via Infotrieve]
  82. Houston P, Campbell CJ, Svaren J, Milbrandt J, Braddock M. The transcriptional corepressor NAB2 blocks Egr-1-mediated growth factor activation and angiogenesis. Biochem Biophys Res Commun. 2001; 283: 480–486.[CrossRef][Medline] [Order article via Infotrieve]
  83. Lucerna M, Mechtcheriakova D, Kadl A, Schabbauer G, Schafer R, Gruber F, Koshelnick Y, Muller HD, Issbrucker K, Clauss M, Binder BR, Hofer E. NAB2, a corepressor of EGR-1, inhibits vascular endothelial growth factor-mediated gene induction and angiogenic responses of endothelial cells. J Biol Chem. 2003; 278: 11433–11440.[Abstract/Free Full Text]
  84. Vidal F, Aragones J, Alfranca A, de Landazuri MO. Up-regulation of vascular endothelial growth factor receptor Flt-1 after endothelial denudation: role of transcription factor Egr-1. Blood. 2000; 95: 3387–3395.[Abstract/Free Full Text]
  85. Grote K, Bavendiek U, Grothusen C, Flach I, Hilfiker-Kleiner D, Drexler H, Schieffer B. Stretch-inducible expression of the angiogenic factor CCN1 in vascular smooth muscle cells is mediated by Egr-1. J Biol Chem. 2004; 279: 55675–55681.[Abstract/Free Full Text]
  86. Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med. 2003; 9: 677–684.[CrossRef][Medline] [Order article via Infotrieve]



This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
F. Hao, M. Tan, X. Xu, and M.-Z. Cui
Histamine Induces Egr-1 Expression in Human Aortic Endothelial Cells via the H1 Receptor-mediated Protein Kinase C{delta}-dependent ERK Activation Pathway
J. Biol. Chem., October 3, 2008; 283(40): 26928 - 26936.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Bhattacharyya, S.-J. Chen, M. Wu, M. Warner-Blankenship, H. Ning, G. Lakos, Y. Mori, E. Chang, C. Nihijima, K. Takehara, et al.
Smad-Independent Transforming Growth Factor-{beta} Regulation of Early Growth Response-1 and Sustained Expression in Fibrosis: Implications for Scleroderma
Am. J. Pathol., October 1, 2008; 173(4): 1085 - 1099.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
J. Danziger
The bone-renal axis in early chronic kidney disease: an emerging paradigm
Nephrol. Dial. Transplant., September 1, 2008; 23(9): 2733 - 2737.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. Nozik-Grayck, H. B. Suliman, S. Majka, J. Albietz, Z. Van Rheen, K. Roush, and K. R. Stenmark
Lung EC-SOD overexpression attenuates hypoxic induction of Egr-1 and chronic hypoxic pulmonary vascular remodeling
Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L422 - L430.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. V. Autieri
Kruppel-Like Factor 4: Transcriptional Regulator of Proliferation, or Inflammation, or Differentiation, or All Three?
Circ. Res., June 20, 2008; 102(12): 1455 - 1457.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
P. R. Reynolds, S. D. Kasteler, M. G. Cosio, A. Sturrock, T. Huecksteadt, and J. R. Hoidal
RAGE: developmental expression and positive feedback regulation by Egr-1 during cigarette smoke exposure in pulmonary epithelial cells
Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1094 - L1101.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
E. Caglayan and S. Rosenkranz
Living on the Edge: Hypoxia-Induced Tissue Damage
Circ. Res., April 25, 2008; 102(8): 864 - 865.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Ding and P. Lengyel
p204 Protein Is a Novel Modulator of Ras Activity
J. Biol. Chem., February 29, 2008; 283(9): 5831 - 5848.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
G. Rokosh
Heme Egr-1: New Partners in Atherosclerotic Progression?
Circ. Res., January 4, 2008; 102(1): 6 - 8.
[Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
W. Xu, C.-L. Chou, H. Sun, H. Fujino, Q. M. Chen, and J. W. Regan
FP Prostanoid Receptor-Mediated Induction of the Expression of Early Growth Response Factor-1 by Activation of a Ras/Raf/Mitogen-Activated Protein Kinase Signaling Cascade
Mol. Pharmacol., January 1, 2008; 73(1): 111 - 118.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
R. Bhindi, R. G. Fahmy, H. C. Lowe, C. N. Chesterman, C. R. Dass, M. J. Cairns, E. G. Saravolac, L.-Q. Sun, and L. M. Khachigian
Brothers in Arms: DNA Enzymes, Short Interfering RNA, and the Emerging Wave of Small-Molecule Nucleic Acid-Based Gene-Silencing Strategies
Am. J. Pathol., October 1, 2007; 171(4): 1079 - 1088.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
G. Woszczek, L.-Y. Chen, S. Nagineni, S. Alsaaty, A. Harry, C. Logun, R. Pawliczak, and J. H. Shelhamer
IFN-{gamma} Induces Cysteinyl Leukotriene Receptor 2 Expression and Enhances the Responsiveness of Human Endothelial Cells to Cysteinyl Leukotrienes
J. Immunol., April 15, 2007; 178(8): 5262 - 5270.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
S. M. Colgan and R. C. Austin
Homocysteinylation of Metallothionein Impairs Intracellular Redox Homeostasis: The Enemy Within!
Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 8 - 11.
[Full Text] [PDF]

Home page
 Circ. Res.Home page
J. M. Simard and V. Gerzanich
Sphingolipids and Transient Receptor Potential Channels: Evolutionarily Ancient Families Now Joined
Circ. Res., June 9, 2006; 98(11): 1347 - 1348.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow