Immunocytochemical evidence for inducible nitric oxide synthase and cyclooxygenase-2 expression with nitrotyrosine formation in human hibernating myocardium - Basic Research in Cardiology
- ️Camici, Paolo G.
- ️Sun Sep 01 2002
Abstract.
Background: Myocardial hibernation may result from repetitive episodes of transient ischaemia leading to prolonged dysfunction. Inducible nitric oxide synthase (iNOS) expression has been demonstrated in animals following brief, non-lethal ischaemia-reperfusion injury. We therefore, hypothesised that in human hibernating myocardium: 1) iNOS would be present; 2) the reaction of nitric oxide and superoxide would form the strong oxidant peroxynitrite; 3) that this process would be accompanied by the expression of cyclooxygenase-2 (Cox-2) which interacts with NOS and whose products could further affect myocardial function. Method and results: In sixteen patients with coronary artery disease (CAD), left ventricular biopsies were obtained from chronically dysfunctional segments subtended by a stenotic artery (> 75 %) and shown to be viable by 18F-fluorodeoxyglucose positron emission tomography. Comparison was made with myocardial biopsies (n = 8) from normally contracting myocardium in patients undergoing coronary surgery, from unused transplant donors and at post-mortem. Regional wall motion score improved in all patients 6 months post-revascularisation (from 2.7 ± 0.7 to 1.5 ± 0.5; p < 0.001), confirming hibernation. Immunocytochemistry localized reactivity to iNOS, Cox-2 and nitrotyrosine (a marker of peroxynitrite formation) to cardiomyocytes from hibernating segments. No difference in reactivity to endothelial NOS was seen between hibernating and control cardiomyocytes. Conclusion: Cox-2 and iNOS are co-expressed in hibernating myocardium with nitrotyrosine suggesting nitric oxide production and peroxynitrite formation. We propose that this is secondary to ischaemia-reperfusion and that the products of these enzymes may have consequences for myocardial contractile function and survival.
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Authors and Affiliations
MRC Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London, W12 ONN United Kingdom, Tel.: +(44) 208 383 3186, Fax: +(44) 208 383 3742, E-Mail: paolo.camici@csc.mrc.ac.uk, , , , , , GB
Paolo G. Camici
Department of Cardiology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London, , , , , , GB
Christopher S. R. Baker & Roger J. C. Hall
Department of Histochemistry, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Chelsea and Westminster Hospital, London, , , , , , GB
Julia M. Polak
MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London, , , , , , GB
David P. Dutka & Ornella Rimoldi
Department of Cardiothoracic Surgery, Queen Elizabeth Hospital, Birmingham, United Kingdom, , , , , , GB
Domenico Pagano, Michael Pitt & Robert S. Bonser
Authors
- Christopher S. R. Baker
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- David P. Dutka
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- Domenico Pagano
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- Ornella Rimoldi
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- Michael Pitt
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- Roger J. C. Hall
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- Julia M. Polak
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- Robert S. Bonser
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- Paolo G. Camici
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Additional information
Received: 11 February 2002, Returned for revision: 14 February 2002, Revision received: 4 March 2002, Accepted: 11 March 2002
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Baker, C., Dutka, D., Pagano, D. et al. Immunocytochemical evidence for inducible nitric oxide synthase and cyclooxygenase-2 expression with nitrotyrosine formation in human hibernating myocardium. Basic Res Cardiol 97, 409–415 (2002). https://doi.org/10.1007/s003950200050
Issue Date: September 2002
DOI: https://doi.org/10.1007/s003950200050