Abstract
This review focuses on the role of advanced glycation end products (AGEs) and its
cell receptor (RAGE) and soluble receptor (sRAGE) in the pathogenesis of chronic lower
limb ischemia (CLLI) and its treatment. CLLI is associated with atherosclerosis in
lower limb arteries. AGE-RAGE axis which comprises of AGE, RAGE, and sRAGE has been
implicated in atherosclerosis and restenosis. It may be involved in atherosclerosis
of lower limb resulting in CLLI. Serum and tissue levels of AGE, and expression of
RAGE are elevated, and the serum levels of sRAGE are decreased in CLLI. It is known
that AGE, and AGE-RAGE interaction increase the generation of various atherogenic
factors including reactive oxygen species, nuclear factor-kappa B, cell adhesion molecules,
cytokines, monocyte chemoattractant protein-1, granulocyte macrophage-colony stimulating
factor, and growth factors. sRAGE acts as antiatherogenic factor because it reduces
the generation of AGE-RAGE-induced atherogenic factors. Treatment of CLLI should be
targeted at lowering AGE levels through reduction of dietary intake of AGE, prevention
of AGE formation and degradation of AGE, suppression of RAGE expression, blockade
of AGE-RAGE binding, elevation of sRAGE by upregulating sRAGE expression, and exogenous
administration of sRAGE, and use of antioxidants. In conclusion, AGE-RAGE stress defined
as a shift in the balance between stressors (AGE, RAGE) and antistressor (sRAGE) in
favor of stressors, initiates the development of atherosclerosis resulting in CLLI.
Treatment modalities would include reduction of AGE levels and RAGE expression, RAGE
blocker, elevation of sRAGE, and antioxidants for prevention, regression, and slowing
of progression of CLLI.
Keywords
advanced glycation end products (AGE) - cell receptor for AGE - soluble receptor for
AGE - AGE-RAGE stress - chronic lower limb ischemia - atherosclerosis - treatment
of chronic lower limb ischemia
