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Keywords:

  • Advanced glycation end products;
  • chronic heart failure;
  • chronic obstructive pulmonary disease;
  • inflammation;
  • N-terminal pro-brain natriuretic peptide;
  • soluble receptor for advanced glycation end products

Abstract

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.