INTRODUCCIÓN: REVISIÓN CRITICA DEL PROBLEMA

Introduction
RESULTADOS
Advanced glycation end-products (AGEs) are molecules that appear in plasma
and tissues and are generated non-enzymatically by glycation and oxidation of
proteins as a consequence of the Maillard reaction, which is driven by oxidative
stress in its final step 73 . Thus an increase in AGEs can be determined
fundamentally by two factors: the existence of chronic hyperglycaemia and/or a
high degree of oxidative stress 278 , while the pathophysiological role of AGEs in
cardiovascular disease is not limited to diabetic patients 92 .
Activation of different pathways implicated in cardiovascular diseases by AGEs
can occur via a specific receptor (RAGE) or independently of RAGE 72 . RAGE has
a C-truncated secretory isoform, soluble RAGE (sRAGE) that circulates in plasma
and has at least two variants: one that is secreted from cells, endogenously
secreted RAGE (esRAGE), and the other which is formed by proteolytic cleavage
from the cell-surface by matrix metalloproteinases, cleaved-RAGE (cRAGE) 279 .
In recent years the role of AGEs in the pathogenesis of cardiovascular diseases
has become recognized. AGEs have been implicated in vascular and myocardial
dysfunction, both diastolic and systolic 95,280 , and in the development of
atherosclerosis 243,281,282 . Evidence of the role of sRAGE in cardiovascular disease,
however, is much less clear. Several studies have shown that esRAGE has a
protective role in cardiovascular disease 164 , but in contrast the significance of total
sRAGE is unclear. In patients without cardiovascular disease, sRAGE has been
proposed to have an atheroscleroticprotective function, in particular by its acting
as a decoy for AGE 283,284 . However, in patients with cardiovascular disease the
role of sRAGE is poorly defined 285,286 .
Little is known about the role of the AGE–RAGE system in heart failure (HF) 248,287 .
In particular, to date only one study has been conducted on the prognostic value of
sRAGE in patients with chronic HF (CHF) 175 . The current study, therefore, aimed
to evaluate the role of the AGE–RAGE system in HF, by analysing glycated
albumin, fluorescent AGE and total sRAGE levels, and any
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