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Early growth response-1 in the pathogenesis of cardiovascular disease

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Abstract

This article reviews the regulatory roles of the immediate-early gene product and prototypic zinc finger transcription factor, early growth response-1 in models of cardiovascular pathobiology, focusing on insights using microRNA, DNAzymes, small hairpin RNA, small interfering RNA, oligonucleotide decoy strategies and mice deficient in early growth response-1.

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References

  1. Cao XM, Koski RA, Gashler A, McKiernan M, Morris CF, Gaffney R, Hay RV, Sukhatme VP (1990) Identification and characterization of the Egr-1 gene product, a DNA-binding zinc finger protein induced by differentiation and growth signals. Mol Cell Biol 10:1931–1939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Christy B, Nathans D (1989) Functional serum response elements upstream of the growth factor-inducible gene, zif268. Mol Cell Biol 9:4889–4895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lau LF, Nathans D (1987) 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 84:1182–1186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lim RW, Varnum BC, Herschman HR (1987) Cloning of tetradecanoyl phorbol ester-induced ‘primary response’ sequences and their expression in density-arrested Swiss 3T3 cells and a TPA non-proliferative variant. Oncogene 1:263–270

    CAS  PubMed  Google Scholar 

  5. Milbrandt J (1987) A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor. Science 238:797–799

    Article  CAS  PubMed  Google Scholar 

  6. Lemaire P, Revelant O, Bravo R, Charnay P (1988) 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 85:4691–4695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gashler A, Sukhatme V (1995) Early growth response protein 1 (Egr-1): prototype of a zinc-finger family of transcription factors. Prog Nucl Acid Res 50:191–224

    Article  CAS  Google Scholar 

  8. McCaffrey TA, Fu C, Du C, Eskinar S, Kent KC, Bush H Jr, Kreiger K, Rosengart T, Cybulsky MI, Silverman ES et al (2000) High-level expression of Egr-1 and Egr-1-inducible genes in mouse and human atherosclerosis. J Clin Invest 105:653–662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sternberg Z, Ghanim H, Gillotti KM, Tario JD Jr, Munschauer F, Curl R, Noor S, Yu J, Ambrus JL Sr, Wallace P et al (2013) Flow cytometry and gene expression profiling of immune cells of the carotid plaque and peripheral blood. Atherosclerosis 229:338–347

    Article  CAS  PubMed  Google Scholar 

  10. van der Feen DE, Dickinson MG, Bartelds B, Borgdorff MA, Sietsma H, Levy M, Berger RM (2015) Egr-1 identifies neointimal remodeling and relates to progression in human pulmonary arterial hypertension. J Heart Lung Transplant 35:481–490

    Article  PubMed  Google Scholar 

  11. Khachigian LM, Lindner V, Williams AJ, Collins T (1996) Egr-1-induced endothelial gene expression: a common theme in vascular injury. Science 271:1427–1431

    Article  CAS  PubMed  Google Scholar 

  12. Christy B, Nathans D (1989) DNA binding site of the growth factor-inducible protein Zif268. Proc Natl Acad Sci U S A 86:8737–8741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cao X, Mahendran R, Guy GR, Tan YH (1993) Detection and characterization of cellular EGR-1 binding to its own recognition site. J Biol Chem 268:16949–16957

    CAS  PubMed  Google Scholar 

  14. Joseph LJ, Le Beau MM, Jamieson GA Jr, Acharya S, Shows T, Rowley JD, Sukhatme VP (1988) Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with “zinc-binding finger” structure. Proc Natl Acad Sci U S A 85:7164–7168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Patwardhan S, Gashler A, Siegel MG, Chang LC, Joseph LJ, Shows TB, Le Beau MM, Sukhatme VP (1991) EGR3, a novel member of the Egr family of genes encoding immediate-early transcription factors. Oncogene 6:917–928

    CAS  PubMed  Google Scholar 

  16. Crosby SD, Veile RA, Donis-Keller H, Baraban JM, Bhat RV, Simburger KS, Milbrandt J (1992) Neural-specific expression, genomic structure, and chromosomal localization of the gene encoding the zinc-finger transcription factor NGFI-C. Proc Natl Acad Sci U S A 89:4739–4743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fu M, Zhu X, Zhang J, Liang J, Lin Y, Zhao L, Ehrengruber MU, Chen YE (2003) Egr-1 target genes in human endothelial cells identified by microarray analysis. Gene 315:33–41

    Article  CAS  PubMed  Google Scholar 

  18. Fang F, Shangguan AJ, Kelly K, Wei J, Gruner K, Ye B, Wang W, Bhattacharyya S, Hinchcliff ME, Tourtellotte WG et al (2013) Early growth response 3 (Egr-3) is induced by transforming growth factor-beta and regulates fibrogenic responses. Am J Pathol 183:1197–1208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Arner E, Daub CO, Vitting-Seerup K, Andersson R, Lilje B, Drablos F, Lennartsson A, Ronnerblad M, Hrydziuszko O, Vitezic M et al (2015) Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science 347:1010–1014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang B, Chen J, Santiago FS, Janes M, Kavurma MM, Chong BH, Pimanda JE, Khachigian LM (2010) Phosphorylation and acetylation of histone H3 and autoregulation by early growth response 1 mediate interleukin-1beta induction of early growth response 1 transcription. Arterioscler Thromb Vasc Biol 30:536–545

    Article  CAS  PubMed  Google Scholar 

  21. Sukhatme VP, Cao X, Chang LL, Tsai-Morris C-H, Stamenkovich D, Ferreira PCP, Cohen DR, Edwards SA, Shows TB, Curran T et al (1988) A zinc-finger encoding gene corregulated with c-Fos during growth and differentiation and after depolarization. Cell 53:37–43

    Article  CAS  PubMed  Google Scholar 

  22. Chen J, Liu MY, Parish CR, Chong BH, Khachigian L (2011) Nuclear import of early growth response-1 involves importin-7 and the novel nuclear localization signal serine-proline-serine. Int J Biochem Cell Biol 43:905–912

    Article  CAS  PubMed  Google Scholar 

  23. Russo MW, Sevetson BR, Milbrandt J (1995) Identification of NAB-1, a repressor of NGFI-A- and Krox20-mediated transcription. Proc Natl Acad Sci U S A 92:6873–6877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Svaren J, Sevetson BR, Apel ED, Zimonjic DB, Popescu NC, Milbrandt J (1996) NAB2, a corepressor of NGFI-A (Egr-1) and Krox20, is induced by proliferative and differentiative stimuli. Mol Cell Biol 16:3545–3553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Silverman ES, Du J, Williams AJ, Wadgaonkar R, Drazen JM, Collins T (1998) cAMP-response-element-binding-protein-binding protein (CBP) and p300 are transcriptional co-activators of early growth response factor-1 (Egr-1). Biochem J 336(Pt 1):183–189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bae MH, Jeong CH, Kim SH, Bae MK, Jeong JW, Ahn MY, Bae SK, Kim ND, Kim CW, Kim KR et al (2002) Regulation of Egr-1 by association with the proteasome component C8. Biochim Biophys Acta 1592:163–167

    Article  CAS  PubMed  Google Scholar 

  27. Yu J, de Belle I, Liang H, Adamson ED (2004) Coactivating factors p300 and CBP are transcriptionally crossregulated by Egr1 in prostate cells, leading to divergent responses. Mol Cell 15:83–94

    Article  CAS  PubMed  Google Scholar 

  28. Yu J, Zhang SS, Saito K, Williams S, Arimura Y, Ma Y, Ke Y, Baron V, Mercola D, Feng GS et al (2009) PTEN regulation by Akt-EGR1-ARF-PTEN axis. EMBO J 28:21–33

    Article  PubMed  Google Scholar 

  29. Manente AG, Pinton G, Tavian D, Lopez-Rodas G, Brunelli E, Moro L (2011) Coordinated sumoylation and ubiquitination modulate EGF induced EGR1 expression and stability. PLoS One 6:e25676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Vedantham S, Thiagarajan D, Ananthakrishnan R, Wang L, Rosario R, Zou YS, Goldberg I, Yan SF, Schmidt AM, Ramasamy R (2014) Aldose reductase drives hyperacetylation of Egr-1 in hyperglycemia and consequent upregulation of proinflammatory and prothrombotic signals. Diabetes 63:761–774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Khachigian LM, Williams AJ, Collins T (1995) Interplay of Sp1 and Egr-1 in the proximal PDGF-A promoter in cultured vascular endothelial cells. J Biol Chem 270:27679–27686

    Article  CAS  PubMed  Google Scholar 

  32. Chapman NR, Perkins ND (2000) Inhibition of the RelA(p65) NF-kappaB subunit by Egr-1. J Biol Chem 275:4719–4725

    Article  CAS  PubMed  Google Scholar 

  33. Snyder R, Thekkumkara T (2013) Interplay between EGR1 and SP1 is critical for 13-cis retinoic acid-mediated transcriptional repression of angiotensin type 1A receptor. J Mol Endocrinol 50:361–374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Li Y, McRobb LS, Khachigian LM (2016) MicroRNA miR-191 targets the zinc finger transcription factor Egr-1 and suppresses intimal thickening after carotid injury. Int J Cardiol 212:229–302

    Article  Google Scholar 

  35. Cheng Y, Liu X, Yang J, Lin Y, Xu DZ, Lu Q, Deitch EA, Huo Y, Delphin ES, Zhang C (2009) MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res 105:158–166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Liu X, Cheng Y, Zhang S, Lin Y, Yang J, Zhang C (2009) A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res 104:476–487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Xu F, Ahmed AS, Kang X, Hu G, Liu F, Zhang W, Zhou J (2015) MicroRNA-15b/16 attenuates vascular neointima formation by promoting the contractile phenotype of vascular smooth muscle through targeting YAP. Arterioscler Thromb Vasc Biol 35:2145–2152

    Article  CAS  PubMed  Google Scholar 

  38. Chen Q, Yang F, Guo M, Wen G, Zhang C, le Luong A, Zhu J, Xiao Q, Zhang L (2015) miRNA-34a reduces neointima formation through inhibiting smooth muscle cell proliferation and migration. J Mol Cell Cardiol 89:75–86

    Article  CAS  PubMed  Google Scholar 

  39. Wang YS, Wang HY, Liao YC, Tsai PC, Chen KC, Cheng HY, Lin RT, Juo SH (2012) MicroRNA-195 regulates vascular smooth muscle cell phenotype and prevents neointimal formation. Cardiovasc Res 95:517–526

    Article  CAS  PubMed  Google Scholar 

  40. Santoro SW, Joyce GF (1997) A general purpose RNA-cleaving DNA enzyme. Proc Natl Acad Sci U S A 94:4262–4266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Cho EA, Moloney FJ, Cai H, Au-Yeung A, China C, Scolyer RA, Yosufi B, Raftery MJ, Deng JZ, Morton SW et al (2013) Safety and tolerability of an intratumorally injected DNAzyme, Dz13, in patients with nodular basal-cell carcinoma: a phase 1 first-in-human trial (DISCOVER). Lancet 381:1835–1843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Cao Y, Yang L, Jiang W, Wang X, Liao W, Tan G, Liao Y, Qiu Y, Feng D, Tang F et al (2014) Therapeutic evaluation of Epstein-Barr Virus-encoded latent membrane protein-1 targeted DNAzyme for treating of nasopharyngeal carcinomas. Mol Ther 22:371–377

    Article  CAS  PubMed  Google Scholar 

  43. Liao WH, Yang LF, Liu XY, Zhou GF, Jiang WZ, Hou BL, Sun LQ, Cao Y, Wang XY (2014) DCE-MRI assessment of the effect of Epstein-Barr virus-encoded latent membrane protein-1 targeted DNAzyme on tumor vasculature in patients with nasopharyngeal carcinomas. BMC Cancer 14:835

    Article  PubMed  PubMed Central  Google Scholar 

  44. Krug N, Hohlfeld JM, Kirsten AM, Kornmann O, Beeh KM, Kappeler D, Korn S, Ignatenko S, Timmer W, Rogon C et al (2015) Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme. N Engl J Med 372:1987–1995

    Article  PubMed  Google Scholar 

  45. Santiago FS, Lowe HC, Kavurma MM, Chesterman CN, Baker A, Atkins DG, Khachigian LM (1999) New DNA enzyme targeting Egr-1 mRNA inhibits vascular smooth muscle proliferation and regrowth factor injury. Nat Med 5:1264–1269

    Article  CAS  PubMed  Google Scholar 

  46. Lowe HC, Chesterman CN, Khachigian LM (2002) Catalytic antisense DNA molecules targeting Egr-1 inhibit neointima formation following permanent ligation of rat common carotid arteries. Thromb Haemost 87:134–140

    CAS  PubMed  Google Scholar 

  47. Lowe HC, Fahmy RG, Kavurma MM, Baker A, Chesterman CN, Khachigian LM (2001) Catalytic oligodeoxynucleotides define a key regulatory role for early growth response factor-1 in the porcine model of coronary in-stent restenosis. Circ Res 89:670–677

    Article  CAS  PubMed  Google Scholar 

  48. Liu GN, Teng YX, Yan W (2008) Transfected synthetic DNA enzyme gene specifically inhibits Egr-1 gene expression and reduces neointimal hyperplasia following balloon injury in rats. Int J Cardiol 129:118–124

    Article  PubMed  Google Scholar 

  49. Wang TR, Yang G, Liu GN (2013) DNA enzyme ED5 depletes egr-1 and inhibits neointimal hyperplasia in rats. Cardiology 125:192–200

    Article  CAS  PubMed  Google Scholar 

  50. Liu QF, Yu HW, You L, Liu MX, Li KY, Tao GZ (2013) Apelin-13-induced proliferation and migration induced of rat vascular smooth muscle cells is mediated by the upregulation of Egr-1. Biochem Biophys Res Commun 439:235–240

    Article  CAS  PubMed  Google Scholar 

  51. Zhang J, Guo C, Wang R, Huang L, Liang W, Liu R, Sun B (2013) An Egr-1-specific DNAzyme regulates Egr-1 and proliferating cell nuclear antigen expression in rat vascular smooth muscle cells. Exp Ther Med 5:1371–1374

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Liu C, Zhang X, Wang S, Cheng M, Liu C, Wang S, Hu X, Zhang Q (2013) Transfected early growth response gene-1 DNA enzyme prevents stenosis and occlusion of autogenous vein graft in vivo. Biomed Res Int 2013:310406

    PubMed  PubMed Central  Google Scholar 

  53. Bhindi R, Khachigian LM, Lowe HC (2006) DNAzymes targeting the transcription factor Egr-1 reduce myocardial infarct size following ischemia-reperfusion in rats. J Thromb Haemost 4:1479–1483

    Article  CAS  PubMed  Google Scholar 

  54. Bhindi R, Fahmy RG, McMahon AC, Khachigian LM, Lowe HC (2012) Intracoronary delivery of DNAzymes targeting human EGR-1 reduces infarct size following myocardial ischaemia reperfusion. J Pathol 227:157–164

    Article  CAS  PubMed  Google Scholar 

  55. Somasuntharam I, Yehl K, Carroll SL, Maxwell JT, Martinez MD, Che PL, Brown ME, Salaita K, Davis ME (2016) Knockdown of TNF-alpha by DNAzyme gold nanoparticles as an anti-inflammatory therapy for myocardial infarction. Biomaterials 83:12–22

    Article  CAS  PubMed  Google Scholar 

  56. Rayner B, Figtree G, Sabaretnam T, Shang P, Mazhar J, Weaver J, Lay W, Witting PK, Hunyor S, Grieve S et al (2013) Selective inhibition of Egr-1 using catalytic oligonucleotides reduces myocardial injury and improves LV systolic function in a preclinical model of myocardial infarction. J Am Heart Assoc 2:e000023

    Article  PubMed  PubMed Central  Google Scholar 

  57. Dickinson MG, Kowalski PS, Bartelds B, Borgdorff MA, van der Feen D, Sietsma H, Molema G, Kamps JA, Berger RM (2014) A critical role for Egr-1 during vascular remodelling in pulmonary arterial hypertension. Cardiovasc Res 103:573–584

    Article  CAS  PubMed  Google Scholar 

  58. Nakamura H, Isaka Y, Tsujie M, Rupprecht HD, Akagi Y, Ueda N, Imai E, Hori M (2002) 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 9:495–502

    Article  CAS  PubMed  Google Scholar 

  59. Ho LC, Sung JM, Shen YT, Jheng HF, Chen SH, Tsai PJ, Tsai YS (2016) Egr-1 deficiency protects from renal inflammation and fibrosis. J Mol Med (Berl). doi:10.1007/s00109-016-1403-6

  60. Chen SH, Yao HW, Chen IT, Shieh B, Li C (2008) Suppression of transcription factor early growth response 1 reduces herpes simplex virus lethality in mice. J Clin Invest 118:3470–3477

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Yao HW, Chen SH, Li C, Tung YY, Chen SH (2012) Suppression of transcription factor early growth response 1 reduces herpes simplex virus 1-induced corneal disease in mice. J Virol 86:8559–8567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Fahmy RG, Dass CR, Sun LQ, Chesterman CN, Khachigian LM (2003) Transcription factor Egr-1 supports FGF-dependent angiogenesis during neovascularization and tumor growth. Nat Med 9:1026–1032

    Article  CAS  PubMed  Google Scholar 

  63. Chen L, Wang S, Zhou Y, Wu X, Entin I, Epstein J, Yaccoby S, Xiong W, Barlogie B, Shaughnessy JD Jr et al (2010) Identification of early growth response protein 1 (EGR-1) as a novel target for JUN-induced apoptosis in multiple myeloma. Blood 115:61–70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ni J, Waldman A, Khachigian LM (2010) c-Jun regulates shear- and injury-inducible Egr-1 expression, vein graft stenosis after autologous end-to-side transplantation in rabbits and intimal hyperplasia in human saphenous veins. J Biol Chem 285:4038–4048

    Article  CAS  PubMed  Google Scholar 

  65. Vazquez-Padron RI, Mateu D, Rodriguez-Menocal L, Wei Y, Webster KA, Pham SM (2010) Novel role of Egr-1 in nicotine-related neointimal formation. Cardiovasc Res 88:296–303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kong L, Shen X, Lin L, Leitges M, Rosario R, Zou YS, Yan SF (2013) PKCbeta promotes vascular inflammation and acceleration of atherosclerosis in diabetic ApoE null mice. Arterioscler Thromb Vasc Biol 33:1779–1787

    Article  CAS  PubMed  Google Scholar 

  67. Chen J, Xu L, Chen S, Yang J, Jiang H (2012) Transcriptional regulation of platelet-derived growth factor-B chain by thrombin in endothelial cells: involvement of Egr-1 and CREB-binding protein. Mol Cell Biochem 366:81–87

    Article  CAS  PubMed  Google Scholar 

  68. Maekawa T, Takahashi N, Honda T, Yonezawa D, Miyashita H, Okui T, Tabeta K, Yamazaki K (2010) Porphyromonas gingivalis antigens and interleukin-6 stimulate the production of monocyte chemoattractant protein-1 via the upregulation of early growth response-1 transcription in human coronary artery endothelial cells. J Vasc Res 47:346–354

    Article  CAS  PubMed  Google Scholar 

  69. Abdel-Malak NA, Mofarrahi M, Mayaki D, Khachigian LM, Hussain SN (2009) Early growth response-1 regulates angiopoietin-1-induced endothelial cell proliferation, migration, and differentiation. Arterioscler Thromb Vasc Biol 29:209–216

    Article  CAS  PubMed  Google Scholar 

  70. Brindle NP, Saharinen P, Alitalo K (2006) Signaling and functions of angiopoietin-1 in vascular protection. Circ Res 98:1014–1023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Egashira K, Suzuki J, Ito H, Aoki M, Isobe M, Morishita R (2008) Long-term follow up of initial clinical cases with NF-kappaB decoy oligodeoxynucleotide transfection at the site of coronary stenting. J Gene Med 10:805–809

    Article  CAS  PubMed  Google Scholar 

  72. Ohtani K, Egashira K, Usui M, Ishibashi M, Hiasa KI, Zhao Q, Aoki M, Kaneda Y, Morishita R, Takeshita A (2004) Inhibition of neointimal hyperplasia after balloon injury by cis-element ‘decoy’ of early growth response gene-1 in hypercholesterolemic rabbits. Gene Ther 11:126–132

    Article  CAS  PubMed  Google Scholar 

  73. Peroulis M, Kakisis J, Kapelouzou A, Giagini A, Giaglis S, Mantziaras G, Kostomitsopoulos N, Karayannacos P, Macheras A (2010) The role of ex-vivo gene therapy of vein grafts with Egr-1 decoy in the suppression of intimal hyperplasia. Eur J Vasc Endovasc Surg 40:216–223

    Article  CAS  PubMed  Google Scholar 

  74. Wang X, Mei Y, Ji Q, Feng J, Cai J, Xie S (2015) Early growth response gene-1 decoy oligonucleotides inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia of autogenous vein graft in rabbits. Interact Cardiovasc Thorac Surg 21:50–54

    Article  CAS  PubMed  Google Scholar 

  75. Murrell M, Khachigian LM, Ward MR (2011) Divergent roles of NF-kappaB and Egr-1 in flow-dependent restenosis after angioplasty and stenting. Atherosclerosis 214:65–72

    Article  CAS  PubMed  Google Scholar 

  76. Han W, Liu GN (2010) EGR-1 decoy ODNs inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia of balloon-injured arteries in rat. Life Sci 86:234–243

    Article  CAS  PubMed  Google Scholar 

  77. Lee SL, Sadovsky Y, Swirnoff AH, Polish JA, Goda P, Gavrilina G, Milbrandt J (1996) Luteinizing hormone deficiency and female infertility in mice lacking the transcription factor NGF-IA (Egr-1). Science 273:1219–1221

    Article  CAS  PubMed  Google Scholar 

  78. Lee SL, Tourtelotte LC, Wesselscmidt RL, Milbrandt J (1995) Growth and differentiation proceeds normally in cells deficient in the immediate-early gene NGFI-A. J Biol Chem 270:9971–9977

    Article  CAS  PubMed  Google Scholar 

  79. Albrecht C, Preusch MR, Hofmann G, Morris-Rosenfeld S, Blessing E, Rosenfeld ME, Katus HA, Bea F (2010) Egr-1 deficiency in bone marrow-derived cells reduces atherosclerotic lesion formation in a hyperlipidaemic mouse model. Cardiovasc Res 86:321–329

    Article  CAS  PubMed  Google Scholar 

  80. Harja E, Bucciarelli LG, Lu Y, Stern DM, Zou YS, Schmidt AM, Yan SF (2004) Early growth response-1 promotes atherogenesis: mice deficient in early growth response-1 and apolipoprotein E display decreased atherosclerosis and vascular inflammation. Circ Res 94:333–339

    Article  CAS  PubMed  Google Scholar 

  81. Wu X, Cheng J, Li P, Yang M, Qiu S, Liu P, Du J (2010) Mechano-sensitive transcriptional factor Egr-1 regulates insulin-like growth factor-1 receptor expression and contributes to neointima formation in vein grafts. Arterioscler Thromb Vasc Biol 30:471–476

    Article  CAS  PubMed  Google Scholar 

  82. Khachigian LM, Anderson KA, Halnon NJ, Resnick N, Gimbrone MA Jr, Collins T (1997) 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 17:2280–2286

    Article  CAS  PubMed  Google Scholar 

  83. Zhang K, Cao J, Dong R, Du J (2013) Early growth response protein 1 promotes restenosis by upregulating intercellular adhesion molecule-1 in vein graft. Oxid Med Cell Longev 2013:432409

    PubMed  PubMed Central  Google Scholar 

  84. Yuan K, Liang W, Zhang J (2015) A comprehensive analysis of differentially expressed genes and pathways in abdominal aortic aneurysm. Mol Med Rep 12:2707–2714

    CAS  PubMed  Google Scholar 

  85. Shin IS, Kim JM, Kim KL, Jang SY, Jeon ES, Choi SH, Kim DK, Suh W, Kim YW (2009) Early growth response factor-1 is associated with intraluminal thrombus formation in human abdominal aortic aneurysm. J Am Coll Cardiol 53:792–799

    Article  PubMed  Google Scholar 

  86. Charolidi N, Pirianov G, Torsney E, Pearce S, Laing K, Nohturfft A, Cockerill GW (2015) Pioglitazone identifies a new target for aneurysm treatment: role of Egr1 in an experimental murine model of aortic aneurysm. J Vasc Res 52:81–93

    Article  CAS  PubMed  Google Scholar 

  87. Yamashiro Y, Papke CL, Kim J, Ringuette LJ, Zhang QJ, Liu ZP, Mirzaei H, Wagenseil JE, Davis EC, Yanagisawa H (2015) Abnormal mechanosensing and cofilin activation promote the progression of ascending aortic aneurysms in mice. Sci Signal 8:ra105

    Article  PubMed  Google Scholar 

  88. Morawietz H, Ma YH, Vives F, Wilson E, Sukhatme VP, Holtz J, Ives HE (1999) Rapid induction and translocation of Egr-1 in response to mechanical strain in vascular smooth muscle cells. Circ Res 84:678–687

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by funding from the National Health and Medical Research Council (NHMRC) of Australia, National Heart Foundation of Australia and Australian Research Council. LMK is an Australia Fellow of the NHMRC. Drs. Fernando Santiago, Yue Li, and Ahmad Alhendi provided helpful comments.

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    Levon M. Khachigian

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Khachigian, L.M. Early growth response-1 in the pathogenesis of cardiovascular disease. J Mol Med 94, 747–753 (2016). https://doi.org/10.1007/s00109-016-1428-x

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