Egr-1 is a Major Vascular Pathogenic Transcription Factor in Atherosclerosis and Restenosis

  title={Egr-1 is a Major Vascular Pathogenic Transcription Factor in Atherosclerosis and Restenosis},
  author={Florian Blaschke and Dennis Bruemmer and Ronald E. Law},
  journal={Reviews in Endocrine and Metabolic Disorders},
The zinc finger transcription factor Egr-1 (early growth response factor-1), also known as nerve growth factorinduced-A (NGFI-A), zif268, Krox-24 and TIS8 was first identified by Sukhatme and colleagues [1]. It is the prototype of a family of zinc-finger transcription factors, that includes Egr-2, Egr-3 and Egr-4. Egr-1 is rapidly and transiently expressed in many different cell types in response to a variety of extracellular stimuli, including growth factors, cytokines and injurious stimuli [2… 

Regulation of the Early Growth Response Protein-1 in vascular smooth muscle cells

The role of Ca2+ signaling in Ang-IIinduced Egr-1 expression in VSMC is examined and the contribution of STIM-1 or Orai-1 is investigated as well as the associated signalling pathways.

Early Growth Response protein 1 (Egr-1) expression by Insulin-like growth factor 1 (IGF-1) involves MAPKs and PKB pathways

It is shown that IGF-1 stimulates the expression of Egr-1 through ERK1/2/JNK and PI3K/PKB and proposed that ROS generation plays an important role in this response.

Lysophosphatidic Acid Induces Early Growth Response Gene 1 Expression in Vascular Smooth Muscle Cells: CRE and SRE Mediate the Transcription

It is found that LPA markedly induces Egr-1 mRNA and protein in aortic smooth muscle cells (SMCs) and a novel role for CREB in mediating LPA-induced gene expression is established, implying that elevated LPA levels may exacerbate atheromatous lesions.

Early Growth Response Protein 1 Promotes Restenosis by Upregulating Intercellular Adhesion Molecule-1 in Vein Graft

Egr-1 may promote ECs proliferation and result in vein graft restenosis by upregulating the expression of ICAM-1, and could be a target for the prevention of restenotic after CABG surgery.

Transcription factor and kinase-mediated signaling in atherosclerosis and vascular injury

The focus of this review is to summarize the current understanding of a finite group of transcription factors and kinases involved in vascular injury and atherosclerosis, including nuclear factor-κB, early growth response factor-I (Egr-I), activator protein-I, hypoxia inducible factor- Iα (HIF-Iα), homeobox, and T cell factor/lymphoid enhancer factor (Tcf-Lef).

Insulin-like growth-factor-1-induced PKB signaling and Egr-1 expression is inhibited by curcumin in A-10 vascular smooth muscle cells.

Curcumin is a potent inhibitor of key components of the IGF-1-induced mitogenic and proliferative signaling system in VSMC, and it is suggested that curcumin-induced attenuation of these signaling components may constitute a potential mechanism for its vasculoprotective effects.

Attenuation of endothelin-1-induced PKB and ERK1/2 signaling, as well as Egr-1 expression, by curcumin in A-10 vascular smooth muscle cells.

Curcumin is a potent inhibitor of ET-1-induced mitogenic and proliferative signaling events in VSMC and the ability of curcumin to attenuate these events may contribute as a potential mechanism for its cardiovascular protective response.

Role of receptor and non-receptor protein tyrosine kinases in vasoactive peptide-induced signaling

This work investigated whether IGF-1R transactivation plays a similar role in ET-1 and Ang II-induced PKB phosphorylation and hypertrophic responses in VSMC.



Egr-1-Induced Endothelial Gene Expression: A Common Theme in Vascular Injury

These findings implicate Egr-1 in the up-regulated expression of PDGF-B and other potent mediators in mechanically injured arterial endothelial cells.

Egr-1 target genes in human endothelial cells identified by microarray analysis.

Egr-1 Activates Basic Fibroblast Growth Factor Transcription

It is concluded that the astrocyte mitogen, ET-3, stimulates egr-1 transcription through a MAP kinase (Erk) related mechanism, and that EGr-1 transactivates bFGF through a specific noncanonical, Egr- 1 site on the promoter.

Matrix-dependent gene expression of egr-1 and PDGF A regulate angiotensin II-induced proliferation in human vascular smooth muscle cells.

In human vascular smooth muscle cells in culture, Ang II-induced proliferation is mediated via the angiotensin type 1 receptor, dependent on ECM proteins, and regulated by differential gene expression of Egr-1 and PDGF-1.

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

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, indicating that induction of EGr-1 by atherogenic factors may be a key step in coordinating the cellular events that result in vascular lesions.

Angiotensin II type 1 receptor blockade inhibits the expression of immediate-early genes and fibronectin in rat injured artery.

Inhibition of intimal thickening by AT1 receptor blockade may be mediated at least in part by suppression of multiple genes related to cell growth and migration in the very early phase after vascular injury.

Differential Regulation of Early Growth Response Gene-1 Expression by Insulin and Glucose in Vascular Endothelial Cells

Differential regulation of Egr-1 expression by insulin and glucose in vascular cells may be one of the initial key events that plays a crucial role in the development of diabetic vascular complications.

Interplay of Sp1 and Egr-1 in the Proximal Platelet-derived Growth Factor A-Chain Promoter in Cultured Vascular Endothelial Cells (*)

Findings demonstrate that PMA-induced Egr-1 displaces Sp1 from the G+C-rich element and activates expression driven by the PDGF-A proximal promoter in endothelial cells, which may be an important regulatory circuit in the control of inducible gene expression in vascular endothelial Cells.