The role of AGEs and AGE inhibitors in diabetic cardiovascular disease.
Prolonged hyperglycemia, dyslipidemia and oxidative stress in diabetes result in the production and accumulation of AGEs. It is now clear that AGEs contribute to the development and progression of cardiovascular disease in diabetes, as well as other complications. AGEs are thought to act through receptor-independent and dependent mechanisms to promote vascular damage, fibrosis and inflammation associated with accelerated atherogenesis. As a result, novel therapeutic agents to reduce the accumulation of AGEs in diabetes have gained interest as potential cardioprotective approaches. A variety of agents have been developed which are examined in detail in this review. These include aminoguanidine, ALT-946, pyridoxamine, benfotiamine, OPB-9195, alagebrium chloride, N-phenacylthiazolium bromide and LR-90. In addition, it has been demonstrated that a number of established therapies have the ability to reduce the accumulation of AGEs in diabetes including ACE inhibitors, angiotensin receptor antagonists, metformin, peroxisome proliferators receptor agonists, metal chelators and some antioxidants. The fact that many of these inhibitors of AGEs are effective in experimental models, despite their disparate mechanisms of action, supports the keystone role of AGEs in diabetic vascular damage. Nonetheless, the clinical utility of AGE inhibition remains to be firmly established. Optimal metabolic and blood pressure control, that is achieved early and sustained indefinitely, remains the best recourse for inhibition of AGEs until more specific interventions become a clinical reality.[1]References
- The role of AGEs and AGE inhibitors in diabetic cardiovascular disease. Thomas, M.C., Baynes, J.W., Thorpe, S.R., Cooper, M.E. Current drug targets. (2005) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
