PDF herunterladen
Thromb Haemost 2002; 87(01): 134-140
DOI: 10.1055/s-0037-1612956
Review Article
Schattauer GmbH

Catalytic Antisense DNA Molecules Targeting Egr-1 Inhibit Neointima Formation following Permanent Ligation of Rat Common Carotid Arteries

Harry C. Lowe
1   Centre for Thrombosis and Vascular Research, School of Pathology, The University of New South Wales and Department of Haematology, The Prince of Wales Hospital, Sydney, Australia
,
Colin N. Chesterman
1   Centre for Thrombosis and Vascular Research, School of Pathology, The University of New South Wales and Department of Haematology, The Prince of Wales Hospital, Sydney, Australia
,
Levon M. Khachigian
1   Centre for Thrombosis and Vascular Research, School of Pathology, The University of New South Wales and Department of Haematology, The Prince of Wales Hospital, Sydney, Australia
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 23. Juli 2001

Accepted after revision 10. September 2001

Publikationsdatum:
13. Dezember 2017 (online)

Auch verfügbar auf
   Lizenzen und Reprints

Summary

Animal models of neointima (NI) formation have proven useful in gaining insights into the mechanisms of restenosis after coronary angioplasty and stenting, but the events at a molecular level remain incompletely understood. Here, we describe a technically straightforward, rat model of NI formation, involving complete ligation of the common carotid artery and demonstrate the importance of the immediate-early gene and zinc finger transcription factor Egr-1 in this process. Acute cessation of common carotid blood flow by vessel ligation, was followed by the expression of Egr-1 in the arterial media within 3 h and NI formation proximal to the point of ligation at 18 days. Local delivery of catalytic oligodeoxynucleotides (ODN) targeting rat Egr-1 mRNA at the time of ligation reduced both Egr-1 expression and NI formation in this model. In contrast, a scrambled version of this ODN had no inhibitory effect. These studies demonstrate for the first time that arterial intimal thickening following artery ligation is critically-dependent on the activation of Egr-1.

Keywords

Neointima - Egr-1 - oligonucleotide
 

  • References

  • 1 Sousa JE, Costa MA, Abizaid A, Abizaid AS, Feres F, Pinto IM, Seixas AC, Staico R, Mattos LA, Sousa AG, Falotico R, Jaeger J, Popma JJ, Serruys PW. Lack of neointimal proliferation after implantation of sirolimuscoated stents in human coronary arteries. Circulation 2001; 103: 192-5.
    CrossrefPubMedSuche in Google Scholar
  • 2 Anonymous. Heart, stroke and vascular diseases, Australian facts. Australian Institute of Health and Welfare and Heart Foundation of Australia. 1999
    PubMedSuche in Google Scholar
  • 3 Lane DM. Dramatic increase in the use of coronary stents. Am J Cardiol 1999; 84: 1141.
    CrossrefPubMedSuche in Google Scholar
  • 4 Virmani R, Farb A. Pathology of in-stent restenosis. Curr Opin Lipidol 1999; 10: 499-506.
    CrossrefPubMedSuche in Google Scholar
  • 5 Johnson GJ, Griggs TR, Badimon L. The utility of animal models in the preclinical study of interventions to prevent human coronary artery restenosis: analysis and recommendations. On behalf of the Subcommittee on Animal, Cellular and Molecular Models of Thrombosis and Haemostasis of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 1999; 81: 835-43.
    Thieme ConnectPubMedSuche in Google Scholar
  • 6 Wexler BC. Histopathological reactivity of carotid arteries of normotensive spraguedawley vs spontaneously hypertensive rats to ligation injury. Stroke 1979; 10: 674-9.
    CrossrefPubMedSuche in Google Scholar
  • 7 Clowes AW, Reidy MA, Clowes MM. Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium. Lab Invest 1983; 49: 327-33.
    PubMedSuche in Google Scholar
  • 8 Geary RL, Kohler TR, Vergel S, Kirkman TR, Clowes AW. Time course of flow-induced smooth muscle cell proliferation and intimal thickening in endothelialized baboon vascular grafts. Circ Res 1991; 74: 14-23.
    PubMedSuche in Google Scholar
  • 9 Mattsson EJR, Kohler TR, Vergel SM, Clowes AW. Increased blood flow induces regression of intimal hyperplasia. Atheroscler Thromb Vasc Biol 1997; 17: 2245-9.
    CrossrefPubMedSuche in Google Scholar
  • 10 Bassiouny HS, White S, Glagov S, Choi E, Giddens DP, Zarins CK. Anastomotic intimal hyperplasia: mechanical injury or flow induced. J Vasc Surg 1992; 15: 708-17.
    CrossrefPubMedSuche in Google Scholar
  • 11 Harmon KJ, Couper LL, Lindner V. Strain-dependent vascular remodeling phenotypes in inbred mice. Am J Pathol 2000; 156: 1741-8.
    CrossrefPubMedSuche in Google Scholar
  • 12 Kumar A, Lindner V. Remodelling with neointima formation in the mouse carotid artery after cessation of blood flow. Arterioscler Thromb Vasc Biol 1997; 17: 2238-44.
    CrossrefPubMedSuche in Google Scholar
  • 13 Houston P, Dickson M, Ludbrook V, White B, Schwachtgen JL, McVey JH, Mackman N, Reese JM, Corman DG, Campbell C, Braddock M. Fluid shear stress induction of the tissue factor promoter in vitro and in vivo is mediated by Egr-1. Arterioscler Thromb Vasc Biol 1999; 19: 281-9.
    CrossrefPubMedSuche in Google Scholar
  • 14 Khachigian LM, Anderson KR, Halnon NJ, Gimbrone MAJ, Resnick N, 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. Arterioscler Thromb Vasc Biol 1997; 17: 2280-6.
    CrossrefPubMedSuche in Google Scholar
  • 15 Khachigian LM, Collins T. Inducible expression of Egr-1 dependent genes: a paradigm of transcriptional activation in vascular endothelium. Circ Res 1997; 81: 457-61.
    CrossrefPubMedSuche in Google Scholar
  • 16 Santiago FS, Lowe HC, Kavurma MM, Baker A, Atkins D, Chesterman CN, Khachigian LM. Novel DNA enzyme targeting NGFI-A mRNA inhibits vascular smooth muscle proliferation and regrowth after injury. Nat Med 1999; 05: 1264-9.
    CrossrefPubMedSuche in Google Scholar
  • 17 Halasz P, Martin P. A microcomputer-based system for semi-automatic analysis of histological sections. Proceedings of the Royal Microscopic Society 1984; 19: 312.
    PubMedSuche in Google Scholar
  • 18 Simons M, Edelman ER, Rosenberg RD. Antisense proliferating cell nuclear antigen oligonucleotides inhibit intimal hyperplasia in a rat carotid aretry injury model. J Clin Invest 1994; 93: 2351-6.
    CrossrefPubMedSuche in Google Scholar
  • 19 Farrell CLBJ, Kaufman SA, Qian YX, Burgess TL. The uptake and distribution of phosphorothioate oligonucleotides into vascular smooth muscle cells in vitro and in rabbit arteries. Antisense Res Dev 1995; 05 (03) 175-83.
    PubMedSuche in Google Scholar
  • 20 Emanueli C, Salis MB, Chao J, Chao L, Agata J, Lin KF, Munao A, Straino S, Minasi A, Capogrossi MC, Madeddu P. Adenovirus-mediated human tissue kallikrein gene delivery inhibits neointima formation induced by interruption of blood flow in mice. Arterioscler Thromb Vasc Biol 2000; 20: 1459-66.
    CrossrefPubMedSuche in Google Scholar
  • 21 Clowes AW, Reidy MA, Clowes MM. Mechanisms of stenosis after arterial injury. Lab Invest 1983; 49: 208-15.
    PubMedSuche in Google Scholar
  • 22 Schwartz RS. tAnimal models of human coronary restenosis. In: Topol EJ. ed. Textbook of Interventional Cardiology. 2nd ed.. Philadelphia: WB Saunders; 1994: 365-81.
  • 23 Gimbrone MAJ, Topper JN, Nagel T, Anderson KR, Garcia-Cardena G. Endothelial dysfunction, hemodynamic forces and athersclerosis. Ann NY Acad Sci 2000; 902: 230-9.
    PubMedSuche in Google Scholar
  • 24 Topper JN, Gimbrone MA. Blood flow and vascular gene expression: fluid shear stress as a modulator of endothelial phenotype. Mol Med Today 1998; 05: 40-6.
    PubMedSuche in Google Scholar
  • 25 Ross R, Glomset JA. The pathogenesis of atherosclerosis. N Engl J Med 1976; 295: 369-77.
    CrossrefPubMedSuche in Google Scholar
  • 26 Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990’s. Nature 1993; 362: 801-8.
    CrossrefPubMedSuche in Google Scholar
  • 27 von Birgelen C, Kutryk MJ, Serruys PW. Three-Dimensional Intravascular Ultrasound Analysis of Coronary Stent Deployment and In-Stent Neointimal Volume: Current Clinical Practice and the Concepts of TRAPIST, ERASER, and ITALICS. J Invasive Cardiol 1998; 10: 17-26.
    PubMedSuche in Google Scholar
  • 28 Muller DWM, Ellis SG, Topol EJ. Experimental models of coronary artery restenosis. J Am Coll Cardiol 1992; 19: 418-32.
    CrossrefPubMedSuche in Google Scholar
  • 29 Santiago FS, Lowe HC, Day FL, Chesterman CN, Khachigian LM. Egr-1 induction by injury is triggered by release and paracrine activation by fibroblast growth factor 2. Am J Pathol 1999; 154: 937-44.
    CrossrefPubMedSuche in Google Scholar
  • 30 Lowe HC, Chesterman CN, Hopkins AP, Juergens CP, Khachigian LM. Acute, Local Release of Fibroblast Growth Factor (FGF 2), but not Transforming Growth Factor b1 (TGF b1), Following Coronary Stenting. Thromb Haemost. 2000 in press..
    PubMedSuche in Google Scholar
  • 31 Sun LQ, Cairns MJ, Saravolac EG, Baker A, Gerlach WL. Catalytic nucleic acids: from lab to applications. Pharmacol Rev 2000; 52: 325-47.
    PubMedSuche in Google Scholar
  • 32 Kay WJ, Levendag PC, Serruys PW. Radioactive stents delay but do not prevent in-stent neointimal hyperplasia. Circulation 2001; 103: 14-7.
    CrossrefPubMedSuche in Google Scholar