177 - Glypican-4 expression is reduced in the inflammatory plaque shoulder in human atherosclerotic lesions (ID 661)
Abstract
Background and Aims
The glycocalyx is involved in many physiological and pathophysiological processes, including plaque formation. Plaques have two plaque shoulders (PS), of which one usually is more prone to rupture, due to increased inflammation. We focus on glypican-4 and heparan sulfate (HS), and their expression pattern at the PS in atherosclerotic lesions, particularly in relation to inflammatory processes, that are supposed to shed the glycocalyx.
Methods
Carotid plaque specimens from 39 patients undergoing endarterectomy were classified into stable (n=17) and vulnerable (n=22) plaques and analyzed by immunohistochemistry. Infiltration with CD68-positive macrophages was used to identify the more inflamed PS. The proportion of positively stained endothelium for glypican-4 and HS in relation to total PS length was calculated.
Results
The proportion of glypican-4-expressing endothelial cells (ECs) was significantly lower in the more inflamed PS (39.0% vs. 50.1%; p=0.013). The difference was more pronounced in vulnerable (31.1% vs. 50.1%; p=0.005) compared with stable plaques (49.2% vs. 49.9%; p=0.88). A comparison of the inflamed PS between vulnerable and stable plaques showed a lower proportion of glypican-4-positive endothelium in vulnerable plaques (31.1% vs. 49.2%; p=0.002). Additionally, we observed a positive correlation between HS and glypican-4-expressing ECs in the non-inflammatory PS in all plaques (r=0.320, p<0.05) as well as we a negative correlation between CD68 and glypican-4 (r=-0.426; p<0.05) and HS (r=-0.408; p=0.06) in vulnerable plaques in the more inflamed PS.
Conclusions
The proportion of glypican-4-expressing endothelial cells was significantly lower in the more inflamed PS of atherosclerotic lesions. This further supports the hypothesis that an intact glycocalyx may be atheroprotective.
