Plasma sRAGE and N-(carboxymethyl) lysine in patients with CHF and/or COPD

Eur J Clin Invest. 2013 Jun;43(6):562-9. doi: 10.1111/eci.12079. Epub 2013 Apr 17.


Background: Knowledge of the role of the receptor for advanced glycation end products (RAGE), particularly its soluble form (sRAGE), and of its advanced glycation end product (AGE) ligand, N-(carboxymethyl)lysine adducts (CML), is limited in chronic heart failure (CHF) and in chronic obstructive pulmonary disease (COPD). We evaluated whether the AGE/RAGE system is activated in stable CHF and COPD, and whether plasma sRAGE and CML levels are affected by clinical and functional parameters.

Materials and methods: We measured plasma levels of sRAGE and CML using a sandwich enzyme-linked immunosorbent assay (ELISA) in 143 subjects, aged ≥ 65 years, divided into five groups: 58 with CHF, 23 with COPD, 27 with CHF+COPD and 35 controls (17 healthy smokers and 18 healthy nonsmokers). Individuals with diabetes were excluded from the study.

Results: Plasma levels of sRAGE and CML were higher in CHF patients than in controls [sRAGE: 0.48 (0.37-0.83) vs. 0.42 (0.29-0.52) ng/mL, P = 0.01; CML: 1.95 (1.58-2.38) vs. 1.68 (1.43-2.00) ng/mL, P = 0.01]. By contrast, sRAGE and CML were not different between both COPD and CHF+COPD patients and controls (P > 0.05). N-terminal pro-brain natriuretic peptide (Nt-pro BNP) correlated with sRAGE, but not with CML, in the patient groups: CHF (r = 0.43, P < 0.001), COPD (r = 0.77, P < 0.0001) and CHF/COPD (r = 0.43, P = 0.003).

Conclusions: Plasma levels of sRAGE and CML are increased in CHF, but not in COPD patients. The robust association between NT-pro BNP, a diagnostic and prognostic marker in CHF, and sRAGE concentrations might suggest a possible BNP pathway of amplification of inflammation via the AGE/RAGE system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / metabolism
  • Case-Control Studies
  • Chronic Disease
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glycation End Products, Advanced / metabolism*
  • Heart Failure / blood*
  • Heart Failure / complications
  • Humans
  • Lysine / analogs & derivatives*
  • Lysine / metabolism
  • Male
  • Natriuretic Peptide, Brain / metabolism
  • Peptide Fragments / metabolism
  • Pulmonary Disease, Chronic Obstructive / blood*
  • Pulmonary Disease, Chronic Obstructive / complications


  • Biomarkers
  • Glycation End Products, Advanced
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • N(6)-carboxymethyllysine
  • Lysine