The Advanced Glycation End-Products (AGE)-Receptor for AGE System (RAGE): An Inflammatory Pathway Linking Obesity and Cardiovascular Diseases

Abstract

The AGE (advanced glycation end-products)-RAGE (receptor for AGE) system is a pro-inflammatory pathway that contributes to the pathogenesis of obesity and obesity-related cardiovascular disorders (CVD). Circulating AGE and the soluble form of RAGE (sRAGE) has been suggested as a potential biomarker of CVD related to obesity. In this study, we aim to (1) summarize the current knowledge about the role of obesity in the onset and progression of CVD, (2) discuss the role of the AGE-RAGE system as a pathway promoting obesity and linking obesity to CVD, and (3) highlight available strategies for reducing AGE-RAGE system activation and the associated beneficial effects.

Keywords: adipose tissue; advanced glycation end-products; apoptosis; atherosclerosis; cardiovascular diseases; cardiovascular risk; heart failure; inflammation; obesity; oxidative stress; receptor for advanced glycation end-products.

Figure 1

Effects of advanced glycation end-products (AGE)–receptor for AGE (RAGE) pathway on adipose tissue homeostasis. AGE can be produced locally, accumulate, cause local damage, and be released into the bloodstream by apoptotic cells. Adipose tissue may also be a target of AGE produced elsewhere. These AGE can primarily influence adipose tissue homeostasis by activating RAGE. Arrows mean the indicate increase or decrease concentrations. Some of the main pathways affected by RAGE activation are shown in the right box of the figure [89,91,120,121,122,123,124,125,126,127,128,129,130,131,132].

Figure 2

Role of sRAGE as a biomarker in obesity and obesity-related complications [4,5,53,79,80,81,86,87,108,109,110,112,114,116,117,118,119]. BMI, body mass index; VAT, visceral adipose tissue; EAT, epicardial adipose tissue; MS, metabolic syndrome; CVD, cardiovascular diseases; LDL, low-density lipoprotein cholesterol; TG, triglycerides; BP, blood pressure; HDL, high-density cholesterol; FMD, flow-mediated vasodilation; HOMA-IR, homeostatic model of IR; IGT, impaired glucose tolerant. Arrows means a mechanisms is activated or decreased.