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Atherosclerosis and the Hypercholesterolemic AGE-RAGE Axis.
Erick McNair1, Mabood Qureshi1, Kailash Prasad2
1Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Summary
High cholesterol is linked to increased advanced glycation end products (AGEs) and oxidative stress, suggesting the AGE-RAGE axis contributes to atherosclerosis. Higher HDL-C may protect by increasing soluble RAGE (sRAGE).
Area of Science:
- Cardiovascular Research
- Metabolic Syndrome
- Oxidative Stress Biology
Background:
- The interaction between advanced glycation end products (AGEs) and the receptor for advanced glycation end products (RAGE) is implicated in atherosclerosis development.
- Soluble receptors for advanced glycation end products (sRAGE) act as decoys, potentially inhibiting AGE-RAGE mediated pathogenesis.
- Hypercholesterolemia and oxidative stress are key contributors to atherosclerosis, while high-density lipoprotein cholesterol (HDL-C) offers protection.
Purpose of the Study:
- To investigate the correlation between hypercholesterolemia and serum levels of AGEs, AGE/sRAGE ratio, and malondialdehyde (MDA).
- To determine if the atheroprotective effect of HDL-C is associated with sRAGE levels and inversely related to AGEs and the AGE/sRAGE ratio.
Main Methods:
- Serum lipid profiles were analyzed in 100 patients, categorizing them into hypercholesterolemic and normocholesterolemic groups.
- Serum concentrations of AGEs, sRAGE, and MDA were measured in both patient groups.
Main Results:
- Hypercholesterolemic subjects exhibited lower sRAGE levels and higher AGE and AGE/sRAGE levels compared to normocholesterolemic individuals.
- In hypercholesterolemic patients, sRAGE levels positively correlated with HDL-C and negatively with low-density lipoprotein, triglycerides, total cholesterol, and MDA.
- A significant positive correlation was observed between hypercholesterolemia, serum AGEs, AGE/sRAGE ratio, and MDA.
Conclusions:
- Hypercholesterolemia is associated with elevated AGEs, AGE/sRAGE ratio, and MDA, suggesting a role for the AGE-RAGE axis in its pathogenesis.
- The atheroprotective influence of HDL-C may be mediated by increased sRAGE and decreased AGE and AGE/sRAGE levels.
- Further research is warranted to fully elucidate the role of the AGE-RAGE axis in hypercholesterolemia-induced atherosclerosis.
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