The AGE/RAGE axis in diabetes-accelerated atherosclerosis
Karin Jandeleit-Dahm1, Anna Watson, Aino Soro-Paavonen
1Albert Einstein Juvenile Diabetes Research Foundation Centre for Diabetes Complications, Diabetes and Metabolism Division, Baker Heart Research Institute, Melbourne, Victoria, Australia. Karin.jandeleit-dahm@baker.edu.au
Clinical and Experimental Pharmacology & Physiology
|February 23, 2008
Summary
Advanced glycation end-products (AGEs) and the receptor RAGE are implicated in atherosclerosis, especially in diabetes. Targeting RAGE may offer a therapeutic strategy for inflammatory vascular diseases.
Area of Science:
- Vascular Biology
- Diabetology
- Immunology
Background:
- Advanced glycation end-products (AGEs) and their receptor RAGE are increasingly linked to atherosclerosis, particularly in diabetic patients.
- AGE-RAGE interactions activate inflammatory and fibrotic pathways, contributing to tissue injury and vascular disease.
Purpose of the Study:
- To investigate the role of the receptor RAGE in vascular disease, including atherosclerosis and diabetic complications.
- To evaluate RAGE as a potential therapeutic target for inflammatory vascular diseases.
Main Methods:
- Creation and analysis of RAGE knockout (RAGE-/-) mice and transgenic mice overexpressing RAGE in endothelial cells.
- Review of existing evidence on AGEs, RAGE, and their impact on atherosclerosis and renal disease.
Main Results:
- RAGE overexpression exacerbated vascular injury, nephropathy, and retinopathy.
- RAGE deletion provided partial protection against vascular injury, including reduced neointima formation and diabetic nephropathy.
Conclusions:
- RAGE acts as a pro-inflammatory and pro-fibrotic receptor, contributing to vascular pathology.
- RAGE represents a promising therapeutic target for managing diabetes-associated atherosclerosis and other inflammatory vascular conditions.
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