The Journal of Thoracic and Cardiovascular Surgery
Volume 137, Issue 6 , Pages 1508-1514 , June 2009

Selective phosphodiesterase-5 inhibition reduces neointimal hyperplasia in rat carotid arteries after surgical endarterectomy

  • Kristóf Hirschberg, MD

      Affiliations

    • Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
    • Department of Cardiovascular Surgery, Semmelweis University, Budapest, Hungary
    • Corresponding Author InformationAddress for reprints: Kristóf Hirschberg, MD, Experimental Laboratory of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 326, OG 2, 69120 Heidelberg, Germany.
    • ,
  • Tamás Radovits, MD, PhD

      Affiliations

    • Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
    • Department of Cardiovascular Surgery, Semmelweis University, Budapest, Hungary
    • ,
  • Sivakkanan Loganathan

      Affiliations

    • Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
    • ,
  • László Entz, MD, PhD

      Affiliations

    • Department of Cardiovascular Surgery, Semmelweis University, Budapest, Hungary
    • ,
  • Carsten J. Beller, MD

      Affiliations

    • Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
    • ,
  • Marie–Luise Gross, MD

      Affiliations

    • Department of Pathology, University of Heidelberg, Heidelberg, Germany
    • ,
  • Peter Sandner, PhD

      Affiliations

    • Bayer HealthCare, Wuppertal, Germany
    • ,
  • Matthias Karck, MD

      Affiliations

    • Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
    • ,
  • Gábor Szabó, MD, PhD

      Affiliations

    • Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany

Received 23 July 2008 ,Revised 16 September 2008 ,Accepted 13 October 2008.

References 

  1. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991;325:445–453
  2. Szeplaki G, Hirschberg K, Gombos T, Varga L, Prohaszka Z, Dosa E, et al. Early complement activation follows eversion carotid endarterectomy and correlates with the time of clamping of the carotid artery. Mol Immunol. 2008;11:3289–3294
  3. Szabo A, Laki J, Madsen HO, Dosa E, Prohaszka Z, Rugonfalvi-Kiss S, et al. Early rise in serum VEGF and PDGF levels predisposes patients with a normal MBL2 genotype to restenosis after eversion endarterectomy. Stroke. 2007;38:2247–2253
  4. Dosa E, Szabo A, Prohaszka Z, Karadi I, Rugonfalvi-Kiss S, Apor A, et al. Changes in the plasma concentration of soluble thrombomodulin in patients with severe carotid artery stenosis after eversion endarterectomy. Inflamm Res. 2005;54:289–294
  5. Hunter GC, Edgar J Poth Memorial/W.L. Gore and Associates, Inc, Lectureship. The clinical and pathological spectrum of recurrent carotid stenosis. Am J Surg. 1997;174:583–588
  6. Ohwada T, Ishibashi T, Yaoita H, Shindo J, Noji H, Ohkawara H, et al. Different contribution of apoptosis to the antiproliferative effects of L-arginine, enalapril and losartan on neointimal growth inhibition after balloon arterial injury. Circ J. 2002;66:965–971
  7. Beller CJ, Radovits T, Kosse J, Gero D, Szabo C, Szabo G. Activation of the peroxynitrite-poly(adenosine diphosphate-ribose) polymerase pathway during neointima proliferation: a new target to prevent restenosis after endarterectomy. J Vasc Surg. 2006;43:824–830
  8. Melichar VO, Behr-Roussel D, Zabel U, Uttenthal LO, Rodrigo J, Rupin A, et al. Reduced cGMP signaling associated with neointimal proliferation and vascular dysfunction in late-stage atherosclerosis. Proc Natl Acad Sci U S A. 2004;101:16671–16676
  9. Yoon JH, Wu CJ, Homme J, Tuch RJ, Wolff RG, Topol EJ, et al. Local delivery of nitric oxide from an eluting stent to inhibit neointimal thickening in a porcine coronary injury model. Yonsei Med J. 2002;43:242–251
  10. Pearce CG, Najjar SF, Kapadia MR, Murar J, Eng J, Lyle B, et al. Beneficial effect of a short-acting NO donor for the prevention of neointimal hyperplasia. Free Radic Biol Med. 2008;44:73–81
  11. Janssens S, Flaherty D, Nong Z, Varenne O, van Pelt N, Haustermans C, et al. Human endothelial nitric oxide synthase gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation after balloon injury in rats. Circulation. 1998;97:1274–1281
  12. Liu YN, Pan SL, Peng CY, Guh JH, Huang DM, Chang YL, et al. YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] inhibits neointima formation in balloon-injured rat carotid through suppression of expressions and activities of matrix metalloproteinases 2 and 9. J Pharmacol Exp Ther. 2006;316:35–41
  13. Tulis DA, Durante W, Peyton KJ, Chapman GB, Evans AJ, Schafer AI. YC-1, a benzyl indazole derivative, stimulates vascular cGMP and inhibits neointima formation. Biochem Biophys Res Commun. 2000;279:646–652
  14. Yamamoto K, Onoda K, Sawada Y, Fujinaga K, Imanaka-Yoshida K, Yoshida T, et al. Locally applied cilostazol suppresses neointimal hyperplasia and medial thickening in a vein graft model. Ann Thorac Cardiovasc Surg. 2007;13:322–330
  15. Beller CJ, Kosse J, Radovits T, Krempien R, Gross ML, Berger I, et al. Adjunct brachytherapy: a new concept to prevent intimal hyperplasia after surgical endarterectomy?. Eur J Cardiothorac Surg. 2006;29:334–342
  16. Legan E, Sisson JA. Method to denude rat aortic endothelium with saponin for phosphoinositide analysis in vascular smooth muscle. J Pharmacol Methods. 1990;23:31–39
  17. Filippi S, Morelli A, Sandner P, Fibbi B, Mancina R, Marini M, et al. Characterization and functional role of androgen-dependent PDE5 activity in the bladder. Endocrinology. 2007;148:1019–1029
  18. Ehsan A, Sommer F, Schmidt A, Klotz T, Koslowski J, Niggemann S, et al. Nitric oxide pathways in human bladder carcinoma. The distribution of nitric oxide synthases, soluble guanylyl cyclase, cyclic guanosine monophosphate, and nitrotyrosine. Cancer. 2002;95:2293–2301
  19. Beller CJ, Kosse J, Radovits T, Gero D, Krempien R, Gross ML, et al. Poly(ADP-ribose) polymerase inhibition combined with irradiation: a dual treatment concept to prevent neointimal hyperplasia after endarterectomy. Int J Radiat Oncol Biol Phys. 2006;66:867–875
  20. Munzel T, Feil R, Mulsch A, Lohmann SM, Hofmann F, Walter U. Physiology and pathophysiology of vascular signaling controlled by guanosine 3′,5′-cyclic monophosphate-dependent protein kinase [corrected Circulation 2008;108:3165]. Circulation. 2003;108:2172–2183
  21. Yu SM, Hung LM, Lin CC. cGMP-elevating agents suppress proliferation of vascular smooth muscle cells by inhibiting the activation of epidermal growth factor signaling pathway. Circulation. 1997;95:1269–1277
  22. Sinnaeve P, Chiche JD, Gillijns H, Van Pelt N, Wirthlin D, Van De Werf F, et al. Overexpression of a constitutively active protein kinase G mutant reduces neointima formation and in-stent restenosis. Circulation. 2002;105:2911–2916
  23. Sinnaeve P, Chiche JD, Nong Z, Varenne O, Van Pelt N, Gillijns H, et al. Soluble guanylate cyclase alpha(1) and beta(1) gene transfer increases NO responsiveness and reduces neointima formation after balloon injury in rats via antiproliferative and antimigratory effects. Circ Res. 2001;88:103–109
  24. Fukumoto S, Koyama H, Hosoi M, Yamakawa K, Tanaka S, Morii H, et al. Distinct role of cAMP and cGMP in the cell cycle control of vascular smooth muscle cells: cGMP delays cell cycle transition through suppression of cyclin D1 and cyclin-dependent kinase 4 activation. Circ Res. 1999;85:985–991
  25. Fu K, Corbley MJ, Sun L, Friedman JE, Shan F, Papadatos JL, et al. SM16, an orally active TGF-beta type I receptor inhibitor prevents myofibroblast induction and vascular fibrosis in the rat carotid injury model. Arterioscler Thromb Vasc Biol. 2008;28:665–671
  26. Wolf YG, Rasmussen LM, Ruoslahti E. Antibodies against transforming growth factor-beta 1 suppress intimal hyperplasia in a rat model. J Clin Invest. 1994;93:1172–1178
  27. Saura M, Zaragoza C, Herranz B, Griera M, Diez-Marques L, Rodriguez-Puyol D, et al. Nitric oxide regulates transforming growth factor-beta signaling in endothelial cells. Circ Res. 2005;97:1115–1123
  28. Wang S, Wu X, Lincoln TM, Murphy-Ullrich JE. Expression of constitutively active cGMP-dependent protein kinase prevents glucose stimulation of thrombospondin 1 expression and TGF-beta activity. Diabetes. 2003;52:2144–2150
  29. Gurjar MV, Sharma RV, Bhalla RC. eNOS gene transfer inhibits smooth muscle cell migration and MMP-2 and MMP-9 activity. Arterioscler Thromb Vasc Biol. 1999;19:2871–2877
  30. Chiche JD, Schlutsmeyer SM, Bloch DB, de la Monte SM, Roberts JD, Filippov G, et al. Adenovirus-mediated gene transfer of cGMP-dependent protein kinase increases the sensitivity of cultured vascular smooth muscle cells to the antiproliferative and pro-apoptotic effects of nitric oxide/cGMP. J Biol Chem. 1998;273:34263–34271

 This work was partially supported by Bayer HealthCare, Wuppertal, Germany. Peter Sandner, PhD, is an employee of Bayer HealthCare, Wuppertal, Germany.

PII: S0022-5223(08)01723-6

doi: 10.1016/j.jtcvs.2008.10.016

The Journal of Thoracic and Cardiovascular Surgery
Volume 137, Issue 6 , Pages 1508-1514 , June 2009

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