Format

Send to

Choose Destination
Curr Pharm Des. 2008;14(10):979-86.

The role of AGEs in cardiovascular disease.

Author information

1
JDRF Centre for Diabetes Complications, Diabetes and Metabolism Division, Baker Heart Research Institute, PO Box 6492 St Kilda Rd Central, Melbourne 8008, Australia.

Abstract

Advanced glycation end-products (AGEs) are generated in the diabetic milieu, as a result of chronic hyperglycemia and enhanced oxidative stress. These AGEs, via direct and receptor dependent pathways promote the development and progression of cardiovascular disease. AGEs accumulate at many sites of the body including the heart and large blood vessels in diabetes. These modified proteins interact with receptors such as RAGE to induce oxidative stress, increase inflammation by promoting NFkappaB activation and enhance extracellular matrix accumulation. These biological effects translate to accelerated plaque formation in diabetes as well as increased cardiac fibrosis with consequent effects on cardiac function. Strategies to reduce the ligation of AGEs to their receptors such as agents which reduce AGE accumulation, soluble RAGE which acts as a competitive antagonist to the binding of AGEs to RAGE and genetic deletions of RAGE appear to attenuate diabetes associated atherosclerosis. Benefits on cardiac dysfunction with these inhibitors of the AGE/RAGE axis are not as well characterised. In conclusion, therapeutic strategies targeting AGEs appear to have significant clinical potential, often in combination with currently used agents such as inhibitors of the renin-angiotensin system, to reduce the major burden of diabetes, its associated cardiovascular complications.

PMID:
18473849
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Bentham Science Publishers Ltd.
Loading ...
Support Center