We recently demonstrated that circulating MGP [matrix Gla (γ-carboxylated glutamate) protein] levels were associated with left ventricular dysfunction and increased mortality in patients with symptomatic aortic stenosis. We hypothesized that patients with chronic HF (heart failure) would have dysregulated MGP levels. We examined plasma dp-cMGP (non-phosphorylated carboxylated MGP) and dp-ucMGP (non-phosphorylated undercarboxylated MGP) in 179 patients with chronic HF and matched healthy controls as well as the relationship between MGP and cardiac dysfunction as assessed by echocardiographic measurements, inflammation [CRP (C-reactive protein)] and neurohormonal activation [NT-proBNP (N-terminal proB-type natriuretic peptide)] and the prognostic value of MGP levels in relation to mortality in these patients. We found markedly enhanced plasma dp-cMGP and, in particular, of dp-ucMGP in chronic HF with increasing levels with disease severity. Elevated MGP species were associated with ischaemic aetiology, increased CRP and NT-proBNP levels, as well as systolic and diastolic dysfunction. Finally, dp-ucMGP was associated with long-term heart transplant-free survival (n=48) in univariate, but not in multivariate, analysis. However, plasma dp-ucMGP was markedly higher in patients who died because of progression of HF (n=12) and gave prognostic information also in multivariate analysis. In conclusion, a dysregulated MGP system could be involved in left ventricular dysfunction in patients with chronic HF.
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Research Article|
April 15 2011
Circulating levels of non-phosphorylated undercarboxylated matrix Gla protein are associated with disease severity in patients with chronic heart failure
Thor Ueland;
*Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
†Section of Endocrinology, Oslo University Hospital Rikshospitalet, Oslo, Norway
Correspondence: Dr Thor Ueland (email [email protected]).
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Christen P. Dahl;
Christen P. Dahl
*Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
‡Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
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Lars Gullestad;
Lars Gullestad
‡Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
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Svend Aakhus;
Svend Aakhus
‡Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
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Kaspar Broch;
Kaspar Broch
‡Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
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Rita Skåardal;
Rita Skåardal
‡Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
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Cees Vermeer;
Cees Vermeer
§VitaK, Maastricht, The Netherlands
‖Cardiovascular Research Institute (CARIM), Maastricht University, Maastricht, The Netherlands
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Pål Aukrust;
Pål Aukrust
*Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
¶Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
**Faculty of Medicine, University of Oslo, Oslo, Norway
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Leon J. Schurgers
Leon J. Schurgers
§VitaK, Maastricht, The Netherlands
‖Cardiovascular Research Institute (CARIM), Maastricht University, Maastricht, The Netherlands
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Publisher: Portland Press Ltd
Received:
December 03 2010
Revision Received:
February 03 2011
Accepted:
February 04 2011
Accepted Manuscript online:
February 04 2011
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2011 Biochemical Society
2011
Clin Sci (Lond) (2011) 121 (3): 119–127.
Article history
Received:
December 03 2010
Revision Received:
February 03 2011
Accepted:
February 04 2011
Accepted Manuscript online:
February 04 2011
Citation
Thor Ueland, Christen P. Dahl, Lars Gullestad, Svend Aakhus, Kaspar Broch, Rita Skåardal, Cees Vermeer, Pål Aukrust, Leon J. Schurgers; Circulating levels of non-phosphorylated undercarboxylated matrix Gla protein are associated with disease severity in patients with chronic heart failure. Clin Sci (Lond) 1 August 2011; 121 (3): 119–127. doi: https://doi.org/10.1042/CS20100589
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