CARDIOVASCULAR MEDICINE

Paradox of circulating advanced glycation end product concentrations in patients with congestive heart failure and after heart transplantation

A Heidland¹, K ebeková³, A Frangiosa², L S De Santo², M Cirillo², F Rossi², M Cotrufo², A Perna², A Klassen¹, R Schinzel⁴, N G De Santo²

¹ Department of Internal Medicine, University of Wurzburg, Wurzburg, Germany
² Chairs of Nephrology and Heart Surgery, Second University of Naples, Naples, Italy
³ Institute of Preventive and Clinical Medicine, Slovak Medical University, Bratislava, Slovakia
⁴ Institute of Physiological Chemistry, University of Wurzburg, Wurzburg, Germany

Correspondence to:
Correspondence to:
Dr A Heidland
Department of Internal Medicine, University of Wurzburg, Hans-Brandmann-Weg 1, D-97080 Wurzburg, Germany; August.Heidland{at}t-online.de

Objectives: To analyse circulating concentrations of advanced glycation end products (AGEs) in patients with severe congestive heart failure (CHF) and after heart transplantation; to identify the potential contribution of kidney function to plasma AGE concentrations; and to determine whether AGE concentrations and parameters of oxidative stress are interrelated.

Methods and results: Circulating N-(carboxymethyl)lysine (CML) and AGE associated fluorescence (AGE-Fl), lipid peroxidation, and glomerular filtration rate (GFR) were measured in a cross sectional study of 22 patients with advanced CHF, 30 heart transplant recipients, and 20 healthy controls. Compared with the controls, the CHF patients had decreased CML (mean (SEM) 467.8 (20.0) ng/ml v 369.3 (22.3) ng/ml, p < 0.01), AGE-Fl (mean (SEM) 302.2 (13.3) arbitrary units v 204.9 (15.7) arbitrary units, p < 0.01), and GFR (p < 0.01). CML was positively related to decreased total protein and serum albumin and negatively to body mass index (p < 0.01). In contrast, in the heart transplant group, impaired GFR was associated with a notable rise of both CML (mean (SEM) 876.1 (53.1) ng/ml, p < 0.01) and AGE-Fl (mean (SEM) 385.6 (26.1) arbitrary units, p < 0.01). A positive relation between CML and serum albumin (r = 0.394, p < 0.05) and lipofuscin (r = 0.651, p < 0.01) was found.

Conclusions: The contrasting concentration of CML and AGE-Fl between patients with CHF and after heart transplantation in the presence of decreased GFR and oxidative stress are explained by lowered plasma proteins in CHF and higher concentrations in heart transplant recipients. In heart transplant recipients, in addition to myocardial inflammatory processes, immunosuppression may be important for enhanced formation of AGEs.

Abbreviations: AGE, advanced glycation end product; AOPP, advanced oxidation protein product; BMI, body mass index; CHF, congestive heart failure; CML, N-(carboxymethyl)lysine; ELISA, enzyme linked immunosorbent assay; GFR, glomerular filtration rate; TNF , tumour necrosis factor

Keywords: congestive heart failure; heart transplantation; carboxymethyllysine; AGE associated fluorescence; oxidative stress

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