title: Effects of rosuvastatin on ADMA, rhokinase, NADPH oxidase, caveolin-1, hsp 90 and NFkB levels in a rat model of myocardial ischaemia-reperfusion.
abstract: OBJECTIVE
  Endothelial dysfunction, oxidative stress and inflammation are among the most important mechanisms of ischaemia-reperfusion (I/R) injury. Besides their cholesterol-lowering effects, statins are known to provide protection against myocardial dysfunction and vascular endothelial injury via nitric oxide-dependent mechanisms. The aim of this study was to investigate the effects of rosuvastatin on certain intermediates involved in the generation of nitric oxide (asymmetrical dimethyl arginin, ADMA, caveolin-1 and hsp 90), oxidative stress (rhokinase, NADPH oxidase) and inflammation (NFkB), using an in vivo model of myocardial infarction in the rat.
  
  
  METHODS
  Adult male Sprague Dawley rats were divided into three groups (control, I/R and I/R after 15 days of rosuvastatin administration). Reperfusion was applied for 120 min following left anterior descending coronary artery ischaemia for 30 min. Caveolin-1, hsp 90 and NFkB levels were evaluated with the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and ADMA, rhokinase and NADPH oxidase levels were evaluated with ELISA.
  
  
  RESULTS
  While NFkB and hsp 90 levels were higher in the I/R group, their levels were significantly lower in the rosuvastatin group. While ADMA and NADPH oxidase levels significantly increased with I/R, they were lower in the rosuvastatin-treated group, but not statistically significant. Rhokinase levels were significantly lower in the rosuvastatin group. Caveolin-1 levels were not different between the groups.
  
  
  CONCLUSIONS
  Our results suggest that ADMA, rhokinase, NADPH oxidase, hsp 90 and NFkB could facilitate I/R injury, and rosuvastatin significantly reduced levels of these parameters. These results indicate that rosuvastatin may have a protective role in I/R injury via mechanisms targeting inflammation, endothelial dysfunction and oxidative stress.
authors: Department of Cardiovascular Surgery, Faculty of Medicine, University of Firat, Elazig, Turkey. oburma@hotmail.com.
authors: Oktay
authors: O
authors: Burma
authors: Department of Pharmacology, Faculty of Medicine, University of Firat, Elazig, Turkey.
authors: Elif
authors: E
authors: Onat
authors: Department of Cardiovascular Surgery, Faculty of Medicine, University of Firat, Elazig, Turkey.
authors: Ayhan
authors: A
authors: Uysal
authors: Department of Biochemistry, Faculty of Medicine, University of Firat, Elazig, Turkey.
authors: Necip
authors: N
authors: Ilhan
authors: Department of Medical Genetics, Faculty of Medicine, University of Firat, Elazig, Turkey.
authors: Deniz
authors: D
authors: Erol
authors: Department of Biophysics, Faculty of Medicine, University of Firat, Elazig, Turkey.
authors: Mete
authors: M
authors: Ozcan
authors: Department of Pharmacology, Faculty of Medicine, University of Firat, Elazig, Turkey.
authors: Engin
authors: E
authors: Sahna
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051242:Caveolin 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005464:Fluorobenzenes / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D019255:NADPH Oxidases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D005464:Fluorobenzenes; D018841:HSP90 Heat-Shock Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D011743:Pyrimidines; D012333:RNA, Messenger; D013449:Sulfonamides; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D000068718:Rosuvastatin Calcium; D001120:Arginine; D019255:NADPH Oxidases; D054460:rho-Associated Kinases
references: Antioxid Redox Signal. 2011 Oct 1;15(7):1875-93
references: 21091074
references: J Biol Chem. 2001 May 25;276(21):17621-4
references: 11278264
references: Hypertens Res. 2011 Jul;34(7):869-75
references: 21562509
references: Am J Physiol Heart Circ Physiol. 2003 Mar;284(3):H919-26
references: 12424098
references: Circulation. 2003 May 20;107(19):2480-6
references: 12719275
references: J Geriatr Cardiol. 2012 Jun;9(2):180-4
references: 22916066
references: Am J Physiol Heart Circ Physiol. 2001 Jun;280(6):H2489-95
references: 11356603
references: Eur Surg Res. 2013;50(1):1-13
references: 23406839
references: Eur Rev Med Pharmacol Sci. 2013;17(15):2103-10
references: 23884833
references: Circ J. 2003 Apr;67(4):305-11
references: 12655160
references: Ir J Med Sci. 2014 Dec;183(4):539-48
references: 24293295
references: J Korean Med Sci. 2010 Jan;25(1):16-23
references: 20052342
references: Surg Clin North Am. 1992 Feb;72(1):65-83
references: 1731390
references: Circ Res. 2000 Mar 17;86(5):494-501
references: 10720409
references: J Am Soc Nephrol. 2004 Aug;15(8):1983-92
references: 15284284
references: Cardiovasc Res. 2004 Feb 15;61(3):548-58
references: 14962485
references: Coron Artery Dis. 2013 Jun;24(4):334-41
references: 23531479
references: J Stroke Cerebrovasc Dis. 2014 Jul;23(6):1429-39
references: 24529602
references: Vascul Pharmacol. 2008 Oct-Dec;49(4-6):134-40
references: 18692595
references: Am J Physiol Heart Circ Physiol. 2011 Apr;300(4):H1274-81
references: 21297026
references: Adv Drug Deliv Rev. 2009 Apr 28;61(4):310-8
references: 19248813
references: Eur J Pharmacol. 2013 Jul 5;711(1-3):57-62
references: 23648561
references: Am J Cardiol. 2004 Jul 15;94(2):157-61
references: 15246890
references: Brain Res. 2013 Jun 26;1519:87-94
references: 23632378
references: Cardiovasc Res. 2007 Jul 15;75(2):417-25
references: 17559823
references: Circulation. 2002 May 21;105(20):2332-6
references: 12021216
references: Biochem Pharmacol. 2012 Dec 15;84(12):1635-42
references: 23022230
references: Am J Cardiol. 2009 Feb 15;103(4):437-41
references: 19195498
references: Vasc Med. 2005 Jul;10 Suppl 1:S19-25
references: 16444865
references: Cardiovasc Res. 2010 Oct 1;88(1):83-92
references: 20558438
references: J Mol Cell Cardiol. 2007 Feb;42(2):271-9
references: 16839566
references: Clin Hemorheol Microcirc. 2010;45(2-4):161-7
references: 20675896
references: Pharmacol Ther. 2013 Dec;140(3):239-57
references: 23859953
references: Atheroscler Suppl. 2003 Dec;4(4):41-51
references: 14664902
references: Circulation. 2011 Apr 19;123(15):1622-32
references: 21464051
references: Nature. 1998 Apr 23;392(6678):821-4
references: 9580552