INTRODUCCIÓN: REVISIÓN CRITICA DEL PROBLEMA

ANEXOS
and inflammatory activity, and they are even implicated in atrial fibrosis in animal
models.
AGEs promote protein cross-linking which alters protein structure and function, as
in the case of type I collagen and elastin in the extracellular matrix, resulting in
atrial fibrosis. Apart from the changes in the extracellular matrix, resulting in a
decrease of elasticity, AGE–RAGE interaction induces oxidative stress and
activation of intracellular signalling, causing secretion of cytokines, contributing to
inflammation and progression of fibrosis. Atrial fibrosis is a hallmark of
arrhythmogenic structural remodelling. Taken together, these observations support
an important pathophysiological role of AGE–RAGE axis in AF through
inflammation, oxidative stress and atrial fibrosis.
In 2008 Kato et al 2 demonstated in rats that DM promoted atrial structural
remodeling via the activation of the AGEs-RAGE system with upregulating of
connective tissue growth factor. Authors suggested that the inhibition of AGEs
formation could be a novel upstream therapeutic approach for diabetes-related
atrial fibrosis.
Recently, our research group published an article about the evidence of a role of
advanced glycation end products in atrial fibrillation 3 . We demonstrated that AGEs
plasma levels were higher in patients with AF, independently of diabetes presence
of DM, and they positively correlated with atrial dimensions, indicating a role for
the AGE–RAGE axis in the arrhythmogenic structural atrial remodelling.
With these comments we want to emphasize the role that AGEs can play in the
genesis of AF. Probably the interaction between HbA1c and FA is due to the AGE
plasma levels. We thought that this is a very interesting suggestion in terms of
research and development of new therapies (AGEs breakers) for prevention of AF.
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