Journal of Plastic, Reconstructive & Aesthetic Surgery
Volume 63, Issue 10 , Pages 1723-1732 , October 2010

The effect of simvastatin on the survival of ischaemic skin flap: An experimental study in rats

  • Fatih Uygur

      Affiliations

    • Department of Plastic and Reconstructive Surgery and Burn Unit, Gülhane Military Medical Academy and Medical Faculty, Haydarpaşa Training Hospital, Selimiye Mahallesi Tıbbiye Caddesi 34 668, Üsküdar, Istanbul, Turkey
    • Corresponding Author InformationCoresponding author. Tel.: +90 532 504 8831; fax: +90 216 348 78 80.
  • ,
  • Nurettin Noyan

      Affiliations

    • Department of Plastic and Reconstructive Surgery and Burn Unit, Gülhane Military Medical Academy and Medical Faculty, Haydarpaşa Training Hospital, Selimiye Mahallesi Tıbbiye Caddesi 34 668, Üsküdar, Istanbul, Turkey
  • ,
  • Aptullah Hahaolu

      Affiliations

    • Department of Pathology, Gülhane Military Medical Academy and Medical Faculty, Haydarpaşa Training Hospital, Istanbul, Turkey

Received 17 November 2008 ,Accepted 22 October 2009.

References 

  1. Takeda N, Maemura K. Horie S.Thrombomodulin Is a Clock-controlled Gene in Vascular Endothelial Cells. J Biol Chem. November 9, 2007;282:32561–32567
  2. Maruyama I. Thrombomodulin, an endothelial anticoagulant; its structure, function and expression. Jpn Circ J. 1992 Feb;56:187–191
  3. Esmon CT, Owen WG. The discovery of thrombomodulin. J Thromb Haemost. 2004;2:209–213
  4. Van de Wouwer M, Collen D, Conway EM. Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation. Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1374–1383Epub 2004 Jun 3
  5. Uygur F, Noyan N, Çeliköz B, et al. Expression of the endothelial thrombomodulin (TM) on the ischemic rat flap model. Preliminary Study. Ann Plast Surg. 2009 Jun;62:693–698
  6. Ide H, Fujiya S, Aanuma Y. Effects of simvastatin, an HMG-CoA reductase inhibitor, on plasma lipids and steroid hormones. Clin Ther. 1990;12:410–420
  7. Shi J, Wang J, Zheng H. Statins increase thrombomodulin expression and function in human endothelial cells by a nitric oxide-dependent mechanism and counteract tumor necrosis factor alpha-induced thrombomodulin downregulation. Blood Coagul Fibrinolysis. 2003;14:575–585
  8. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arterioscler Thromb Vasc Biol. 2001;21:1712–1719
  9. Ii M, Losordo DW. Statins and the endothelium. Vascul Pharmacol. 2007;46:1–9
  10. Weitz-Schmidt G. Statins as anti-inflammatory agents. Trends Pharmacol Sci. 2002;23:482–486
  11. Schonbeck U, Libby P. Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents?. Circulation. 2004;109:II18–II26
  12. McFarlane RM, Deyong G, Henry RA. The design of a pedicle flap in the rat to study necrosis and its prevention. Plast Reconstr Surg. 1965;35:177
  13. Endres M, Laufs U, Huang Z, et al. Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 1998;95:8880–8885
  14. Laufs U, Marra D, Node K, et al. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors attenuate vascular smooth muscle proliferation by preventing rho GTPase-induced downregulation of p27(Kip1). J Biol Chem. 1999;274:21926–21931
  15. Sparrow CP, Burton CA, Hernandez M, et al. Simvastatin has anti-inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering. Arterioscler Thromb Vasc Biol. 2001;21:115–121
  16. Bea F, Blessing E, Bennett B, et al. Simvastatin promotes atherosclerotic plaque stability in apoEdeficient mice independently of lipid lowering. Arterioscler Thromb Vasc Biol. 2002;22:1832–1837
  17. Bea F, Blessing E, Shelley MI, et al. 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
  18. Uygur F, Evinç R, Uran M, Hahoglu A. ‘Salvaging The Zone of Stasis By Simvastatin: An Experimental Study In Rats’. J Burn Care Res. 2009;30:872–879
  19. Ulkur E, Karagoz H, Ergun O, et al. The Effect of Hyperbaric Oxygen Therapy on the Delay Procedure. Plast Recontr Surg. 2007;119:86
  20. Ozgentas HE, Shenaq S, Spira M. Development of a TRAM flap model in the rat and study of vascular dominance. Plast Reconstr Surg. 1994;94:1012
  21. Von Bülow S, Hartmann T, Fuchs PC, et al. Endothelial thrombomodulin (CD 141) in a rabbit burn model. Burns. 2005 Jun;31:459–464
  22. Tabata M, Sugihara K, Yonezawa S, et al. An immunohistochemical study of thrombomodulin in oral squamous cell carcinoma and its association with invasive and metastatic potential. J Oral Pathol Med. 1997 Jul;26:258–264
  23. Ogawa H, Yonezawa S, Maruyama I, et al. Expression of thrombomodulin in squamous cell carcinoma of the lung: its relationship to lymph node metastasis and prognosis of the patients. Cancer Lett. 2000 Feb 28;149:95–103
  24. Tezuka Y, Yonezawa S, Maruyama I, et al. Expression of thrombomodulin in esophageal squamous cell carcinoma and its relationship to lymph node metastasis. Cancer Res. 1995 Sep 15;55:4196–4200
  25. Hanly AM, Redmond M, Winter DC, et al. Thrombomodulin expression in colorectal carcinoma is protective and correlates with survival. Br J Cancer. 2006 May 8;94:1320–1325
  26. Mohri M, Oka M, Aoki Y, et al. Intravenous extended infusion of recombinant human soluble thrombomodulin prevented tissue factor-induced disseminated intravascular coagulation in rats. Am J Hematol. 1994 Apr;45:298–303
  27. Aoki Y, Ohishi R, Takei R, et al. Effects of recombinant human soluble thrombomodulin (rhs-TM) on a rat model of disseminated intravascular coagulation with decreased levels of plasma antithrombin III. Thromb Haemost. 1994 Apr;71:452–455
  28. Gonda Y, Hirata S, Saitoh K, et al. Antithrombotic effect of recombinant human soluble thrombomodulin on endotoxin-induced disseminated intravascular coagulation in rats. Thromb Res. 1993 Aug 15;71:325–335
  29. Laufs U, La Fata V, Plutzky J, et al. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97:1129–1135
  30. Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J, et al. Effects of the 3-hydroxy-3- methylglutaryl-CoA reductase inhibitors, atorvastatins and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J ClinInvest. 1998;101:2711–2719
  31. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arterioscler Thromb Vasc Biol. 2001;21:1712–1719
  32. Weitz-Schmidt G. Statins as anti-inflammatory agents. Trends Pharmacol Sci. 2002;23:482–486
  33. Schonbeck U, Libby P. Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents?. Circulation. 2004;109:II18–II26
  34. Kureishi Y, Luo Z, Shiojima I, et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med. 2000;6:1004–1010
  35. Rohrich RJ, Cherry GW, Spira M. Enhancement of skin-flap survival using nitroglycerin ointment. Plast Reconstr Surg. 1984 Jun;73:943–948
  36. Rohrich RJ, Handren J, Kersh R, et al. Prevention of microvascular thrombosis with short-term infusion of human tissue-type plasminogen activator. Plast Reconstr Surg. 1996 Jul;98:118–128

PII: S1748-6815(09)00746-3

doi: 10.1016/j.bjps.2009.10.021

Journal of Plastic, Reconstructive & Aesthetic Surgery
Volume 63, Issue 10 , Pages 1723-1732 , October 2010