Exercise for Cardiovascular Disease Prevention and Treatment From Molecular to Clinical, Part 1

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6.7 Effects of Exercise on AGEs-Induced ROS

Glycation is the non-enzymatic covalent bonding to glucose to proteins and lipids.

Chronic hyperglycemia induces glycation and cross-linking of the glycation prod-

ucts to produce AGEs. AGEs can bind to RAGE on endothelial cells and macro-

phages, triggering excessive production of ROS and pro-inflammatory cytokines

[ 157 ]. The exact mechanism of AGE/RAGE-induced ROS generation in not fully

explored; however, evidences suggest an involvement of NADPH oxidase [ 158 ,

159 ]. AGE/RAGE-derived ROS can induce NADPH oxidases and provoke further

ROS production [ 159 ]. It has been also hypothesized that NADPH oxidase-derived

ROS can have similar effect on AGE/RAGE-derived ROS in a positive feedback

loop [ 159 ].

RAGE-expressing human endothelial cells exposed to AGEs exhibited increased

ROS production and expression of tissue factor, pointing to the presence of inflam-

mation [ 158 ]. A recent study by Hou et al. [ 160 ] showed significantly increased

expression of RAGE, nuclear factor-kappa B (NF-κB) and inflammatory cytokines

in the myocardium of diabetic rats.

There are currently scarce data available on the effect of exercise on AGEs and

RAGE in DCM.  However, exercise training has been reported to reduce lipid

peroxidation, ROS, activation of NFκB, interleukin-6 (IL-6) and advanced glyca-

tion in the aortas of aged rats [ 161 ] (Fig. 12.5). This study explained that the

Fig. 12.5 Effect of exercise on hyperglycemia-induced formation of cross-linked AGEs. RAGE
receptor for advanced glycation endproducts, AGEs advanced glycation end-products, NF-κB
nuclear factor-kappa B, sRAGE soluble receptor for advanced glycation endproducts, O 2 •
superoxide

12 Exercise Amaliorates Metabolic Disturbances and Oxidative Stress in Diabetic...