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European Heart Journal Advance Access originally published online on December 21, 2006
European Heart Journal 2007 28(2):269; doi:10.1093/eurheartj/ehl429
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© The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Gamma-glutamyltransferase, leukotrienes, and cardiovascular risk

Magnus Bäck

Department of Cardiology and Center for Molecular Medicine
Karolinska University Hospital L8:03
171 76 Stockholm
Sweden
Tel: +46 8 51770000
Fax: +46 8 313147
E-mail address: magnus.back{at}cmm.ki.se
Member of the ESC Working Group on Pathogenesis of Atherosclerosis (WG 23)

It is with great interest that I read the article ‘Serum gamma-glutamyltransferase predicts myocardial infarction and fatal coronary heart disease among 28 838 middle-aged men and women’ by Lee et al.1 As pointed out by the authors, previous studies have brought the attention to a possible link between gamma-glutamyltransferase and inflammation in atherosclerosis.1 In this context, it can be pointed out that, in addition to effects on glutathione metabolism and redox regulation, the gamma-glutamyltransferase enzyme also uses leukotrienes as substrate.2 Leukotrienes are lipid mediators of inflammation derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. Recent studies have provided evidence for a strong genetic link between this pathway and increased risk of myocardial infarction, and the effects of a leukotriene synthesis inhibitor have been evaluated on biomarkers of cardiovascular risk.3 Experimental studies have implicated the dihydroxy-leukotriene LTB4 in pathophysiological reactions of atherosclerosis and restenosis.4 In addition, increased cysteinyl-leukotriene formation has been detected in subjects with early atherosclerosis.5

Gamma-glutamyltransferase catalyses a transpeptidation of the amino acid side chain of the cysteinyl-leukotrienes.2 This leads to an interconversion of the two vasoactive leukotrienes LTC4 and LTD4, which can influence the pharmacology of leukotriene-induced responses.2 Leukotriene metabolism could hence propose one possible mechanism behind the link between gamma-glutamyltransferase and inflammation in cardiovascular disease.

References

  1. Lee DH, Silventoinen K, Hu G, Jacobs DR Jr, Jousilahti P, Sundvall J, Tuomilehto J. (2006) Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28 838 middle-aged men and women. Eur Heart J 27:2170–2176.[Abstract/Free Full Text]
  2. Bäck M, Kumlin M, Cotgreave IA, Dahlén SE. (2001) An alternative pathway for metabolism of leukotriene D4: effects on contractions to cysteinyl-leukotrienes in the guinea-pig trachea. Br J Pharmacol 133:1134–1144.[CrossRef][Web of Science][Medline]
  3. Hakonarson H, Thorvaldsson S, Helgadottir A, Gudbjartsson D, Zink F, Andresdottir M, Manolescu A, Arnar DO, Andersen K, Sigurdsson A, Thorgeirsson G, Jonsson A, Agnarsson U, Bjornsdottir H, Gottskalksson G, Einarsson A, Gudmundsdottir H, Adalsteinsdottir AE, Gudmundsson K, Kristjansson K, Hardarson T, Kristinsson A, Topol EJ, Gulcher J, Kong A, Gurney M, Stefansson K. (2005) Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: a randomized trial. JAMA 293:2245–2256.[Abstract/Free Full Text]
  4. Bäck M, Bu DX, Branström R, Sheikine Y, Yan ZQ, Hansson GK. (2005) Leukotriene B4 signaling through NF-{kappa}B-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia. Proc Natl Acad Sci USA 102:17501–17506.[Abstract/Free Full Text]
  5. Bäck M, Airila-Månsson S, Jogestrand T, Söder B, Söder P-Ö. (2006) Increased leukotriene concentrations in gingival crevicular fluid from subjects with periodontal disease and atherosclerosis. Atherosclerosis in press.

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This Article
Right arrow FREE Full Text (PDF) Freely available
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28/2/269    most recent
ehl429v1
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