Journal of Cardiac Failure
Volume 16, Issue 4 , Pages 314-319 , April 2010

A Promoter Polymorphism of the Endothelial Nitric Oxide Synthase Gene is Associated With Reduced mRNA and Protein Expression in Failing Human Myocardium

  • Amit A. Doshi, MD

      Affiliations

    • Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH
    • Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH
    • ,
  • Mark T. Ziolo, PhD

      Affiliations

    • Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH
    • Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH
    • ,
  • Honglan Wang, PhD

      Affiliations

    • Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH
    • Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH
    • ,
  • Emily Burke, RN, BSN, CCTC

      Affiliations

    • Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH
    • ,
  • Amanda Lesinski, BS

      Affiliations

    • Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH
    • ,
  • Philip Binkley, MD, MPH

      Affiliations

    • Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH
    • Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH
    • Corresponding Author InformationReprint requests: Philip F. Binkley, MD, MPH, Wilson Professor of Medicine, Professor of Epidemiology, Vice Chair for Academic Affairs, The Ohio State University, Room 221 Means Hall, 1654 Upham Drive, Columbus, OH 43210. Tel: 614-293-8963; Fax: 614-293-5614

Received 2 June 2009 ,Revised 8 December 2009 ,Accepted 17 December 2009.

References 

  1. Cook S. Coronary artery disease, nitric oxide and oxidative stress: the “Yin-Yang” effect–a Chinese concept for a worldwide pandemic. Swiss Med Wkly. 2006;136:103–113
  2. Cooke GE, Doshi A, Binkley PF. Endothelial nitric oxide synthase gene: prospects for treatment of heart disease. Pharmacogenomics. 2007;8:1723–1734
  3. Cooke JP, Losordo DW. Nitric oxide and angiogenesis. Circulation. 2002;105:2133–2135
  4. McNamara DM, Holubkov R, Postava L, Ramani R, Janosko K, Mathier M, et al. Effect of the Asp298 variant of endothelial nitric oxide synthase on survival for patients with congestive heart failure. Circulation. 2003;107:1598–1602
  5. Ziolo MT, Kohr MJ, Wang H. Nitric oxide signaling and the regulation of myocardial function. J Mol Cell Cardiol. 2008;45:625–632
  6. Stein B, Frank P, Schmitz W, Scholz H, Thoenes M. Endotoxin and cytokines induce direct cardiodepressive effects in mammalian cardiomyocytes via induction of nitric oxide synthase. J Mol Cell Cardiol. 1996;28:1631–1639
  7. Binkley PF, Nunziatta E, Liu-Stratton Y, Cooke G. A polymorphism of the endothelial nitric oxide synthase promoter is associated with an increase in autonomic imbalance in patients with congestive heart failure. Am Heart J. 2005;149:342–348
  8. Cai H, Wilcken DE, Wang XL. The Glu-298–>Asp (894G–>T) mutation at exon 7 of the endothelial nitric oxide synthase gene and coronary artery disease. J Mol Med. 1999;77:511–514
  9. Hingorani AD, Liang CF, Fatibene J, Lyon A, Monteith S, Parsons A, et al. A common variant of the endothelial nitric oxide synthase (Glu298–>Asp) is a major risk factor for coronary artery disease in the UK. Circulation. 1999;100:1515–1520
  10. Shimasaki Y, Yasue H, Yoshimura M, Nakayama M, Kugiyama K, Ogawa H, et al. Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction. J Am Coll Cardiol. 1998;31:1506–1510
  11. Marroni AS, Metzger IF, Souza-Costa DC, Nagassaki S, Sandrim VC, Correa RX, et al. Consistent interethnic differences in the distribution of clinically relevant endothelial nitric oxide synthase genetic polymorphisms. Nitric Oxide. 2005;12:177–182
  12. Pfaffl MW. Quantification strategies in real-time PCR. In:  Bustin S editors. A-Z of quantitative PCR. La Jolla, CA: International University Line; 2004;
  13. Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Kugiyama K, Ogawa H, et al. T-786–>C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation. 1999;99:2864–2870
  14. Dosenko VE, Zagoriy VY, Haytovich NV, Gordok OA, Moibenko AA. Allelic polymorphism of endothelial NO-synthase gene and its functional manifestations. Acta Biochim Polon. 2006;53:299–302
  15. Gomma AH, Elrayess MA, Knight CJ, Hawe E, Fox KM, Humphries SE. The endothelial nitric oxide synthase (Glu298Asp and -786T>C) gene polymorphisms are associated with coronary in-stent restenosis. Eur Heart J. 2002;23:1955–1962
  16. Rossi GP, Cesari M, Zanchetta M, Colonna S, Maiolino G, Pedon L, et al. The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study. J Am Coll Cardiol. 2003;41:930–937
  17. Cattaruzza M, Guzik TJ, Slodowski W, Pelvan A, Becker J, Halle M, et al. Shear stress insensitivity of endothelial nitric oxide synthase expression as a genetic risk factor for coronary heart disease. Circ Res. 2004;15:841–847
  18. Fairchild TA, Fulton D, Fontana JT, Gratton JP, McCabe TJ, Sessa WC. Acidic hydrolysis as a mechanism for the cleavage of the Glu(298)–>Asp variant of human endothelial nitric-oxide synthase. J Biol Chem. 2001;276:26674–26679
  19. Kato N, Sugiyama T, Morita H, Nabika T, Kurihara H, Yamori Y, et al. Lack of evidence for association between the endothelial nitric oxide synthase gene and hypertension. Hypertension. 1999;33:933–936
  20. Rossi GP, Maiolino G, Zanchetta M, Sticchi D, Pedon L, Cesari M, et al. The T(-786)C endothelial nitric oxide synthase genotype predicts cardiovascular mortality in high-risk patients. J Am Coll Cardiol. 2006;48:1166–1174
  21. Raman CS, Li H, Martasek P, Kral V, Masters BS, Poulos TL. Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center. Cell. 1998;95:939–950
  22. Tesauro M, Thompson WC, Rogliani P, Qi L, Chaudhary PP, Moss J. Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci U S A. 2000;97:2832–2835
  23. Rossi GP, Cesari M. Reply. J Am Coll Cardiol. 2007;49:1226–1227

 Dr. Philip F. Binkley is supported by National Heart, Lung and Blood Institute/National Institutes of Health Grant K24-HL04208 and the James H. and Ruth J. Wilson Professorship. Dr. Ziolo is supported by National Institutes of Health Grant HL079283 and HLO94692. Dr. Wang is supported by The American Heart Association Post-Doctoral Fellowship 0725560B.

PII: S1071-9164(09)01233-0

doi: 10.1016/j.cardfail.2009.12.013

Journal of Cardiac Failure
Volume 16, Issue 4 , Pages 314-319 , April 2010

Article Tools

* Image Usage & Resolution