# Inflammatory Reactions Within the Epicardial Adipose Tissue Are Associated with the Expression of the Receptor for Advanced Glycation End Products in Aortic Stenosis

## TL;DR

Epicardial adipose tissue in aortic stenosis shows increased inflammation linked to a receptor for advanced glycation end products, suggesting a potential biomarker and treatment target.

## Contribution

This study identifies a novel role of the AGEs-RAGE axis in inflammatory processes within epicardial adipose tissue in aortic stenosis.

## Key findings

- Epicardial adipose tissue volume and RAGE expression are significantly higher in aortic stenosis patients compared to controls.
- Macrophage infiltration in epicardial adipose tissue correlates with RAGE-positive cells and is mediated through the AGEs-RAGE axis.
- EAT volume independently correlates with macrophage activation, but not with the severity of aortic stenosis.

## Abstract

Background: Epicardial adipose tissue (EAT) is a metabolically active organ implicated in coronary artery disease (CAD); however, its role in aortic stenosis (AS) remains unclear. Advanced glycation end products (AGEs) and their receptor (RAGE) promote cardiovascular tissue inflammation. This study aimed to investigate whether inflammatory activity within the EAT, particularly involving the AGEs-RAGE axis, is associated with AS. Methods: We studied 42 patients (isolated AS, n = 15; AS with CAD, n = 15; and CAD alone, n = 12) undergoing surgical intervention, along with 10 autopsy controls. EAT volume was assessed via computed tomography and indexed to body surface area. Furthermore, macrophage infiltration (CD68) and RAGE expression in EAT samples were analyzed using immunohistochemistry and immunofluorescence imaging. Results: EAT volume index was significantly higher in all surgical groups than in the controls (p < 0.001). These surgical groups also had markedly increased CD68- and RAGE-positive cells compared with the controls (p < 0.001), with colocalization detected by means of immunofluorescence imaging. Additionally, the EAT volume index independently and positively correlated with CD68-positive cell counts (p = 0.021), and causal mediation analysis suggested that it promotes CD68-positive macrophage activation through pathways mediated by RAGE-positive cells (p = 0.024). Inflammatory cells did not correlate with AS severity (maximum aortic jet velocity, mean pressure gradient, aortic valve area). Conclusions: EAT in AS exhibits increased macrophage infiltration and RAGE expression. Therefore, the AGEs-RAGE axis may contribute to local inflammatory activity, and EAT can be a potential biomarker and therapeutic target in AS.